RESUMEN
The accidental discovery of a retrotracheal left pulmonary artery in a 4-month-old infant encouraged us to review the various embryologic theories concerning this very rare anomaly and perform an anatomic update in order to better define surgical treatment. Nathan underwent surgery for a bilateral inguinal hernia at the age of 4 months. The postoperative period was marked by malaise associated with dyspnoea, stridor, tachycardia and sweating. A X-ray of the thorax, oesophageal transit and angio scan presented an intertracheo-oesophageal left pulmonary artery and a reimplantation of the left pulmonary artery was successfully performed. A retrotracheal left pulmonary artery is a very rare malformation. From development of pulmonary vascularisation, three embryologic theories have been advanced to explain this anomaly. From an anatomic point of view, Landing et al. proposed in 1982 a classification system of retrotracheal left pulmonary artery. Today, current radiological techniques not only provide a precise diagnosis but also make it possible to define appropriate care for the different types of this malformation.
Asunto(s)
Arteria Pulmonar/anomalías , Anomalías Cardiovasculares/diagnóstico , Diagnóstico por Imagen/métodos , Disnea/etiología , Trastornos de la Motilidad Esofágica/etiología , Trastornos de la Motilidad Esofágica/patología , Retardo del Crecimiento Fetal , Hernia Inguinal/cirugía , Humanos , Hallazgos Incidentales , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Masculino , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/patología , Arteria Pulmonar/embriología , Arteria Pulmonar/cirugía , Reimplantación , Taquicardia/etiología , Traqueomalacia/etiología , Traqueomalacia/patologíaRESUMEN
SUMMARY: Congenital anterior urethrocutaneous fistulas are infrequent. We report a case of a congenital anterior urethrocutaneous fistula associated with a stenosis of the bulbar urethra in the context of a high anorectal malformation. We describe the surgical technique for the reconstruction of the urethra.
Asunto(s)
Canal Anal/anomalías , Fístula Cutánea/congénito , Recto/anomalías , Enfermedades Uretrales/congénito , Fístula Urinaria/congénito , Anomalías Múltiples/cirugía , Canal Anal/cirugía , Fístula Cutánea/cirugía , Humanos , Recién Nacido , Masculino , Recto/cirugía , Enfermedades Uretrales/cirugía , Estrechez Uretral/cirugía , Fístula Urinaria/cirugíaAsunto(s)
Enfermedades del Ovario/diagnóstico , Enfermedades del Ovario/terapia , Adolescente , Servicios de Salud del Adolescente , Carcinoma/diagnóstico , Carcinoma/patología , Carcinoma/terapia , Femenino , Ginecología , Humanos , Estadificación de Neoplasias , Enfermedades del Ovario/patología , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/patología , Neoplasias Ováricas/terapiaRESUMEN
Treatment of carpal tunnel syndrome consists in decompression of the median nerve by section of the flexor retinaculum. Usually, this surgery improves the disease with disappearance of the symptoms. However, some painful sequelae may remain such as painful discharges, paresthesiae or permanent anesthesia of the base of the thumb or of the scar related to an injury of the palmar cutaneous branch of the median nerve (PCBm). This study was performed to define the accurate emergence and the anatomic characteristics of this nerve in relation to stable landmarks. Moreover, it assessed the importance of the visual identification of the branch during section of the flexor retinaculum. Thirty-five hands were dissected under macroscopic examination and under magnification of the thinnest branches. Measurements were performed with a caliper and the forearm in supination. Determination of the bistyloid line showed variability in the location of the distal wrist crease. Thus, it could not be used as a landmark to locate the PCBm. The palmar cutaneous branch is the distal collateral branch of the median nerve in the forearm. It emerges on its radial side, on average 44.3 mm before the bistyloid line. It courses in line with the third finger and perforates the antebrachial aponeurosis about 5.7 mm from the bistyloid line. This emergence can be located in the palm, where it can be injured if the incision is performed in line with the third finger. The PCBm usually ends in the palm by division into two or three branches. The lateral branch supplies the skin of the thenar eminence while the medial, usually shorter branch supplies the midline part of the palm. This study has shown the importance of performing the cutaneous incision in line with the fourth finger to avoid injury to the PCBm.
Asunto(s)
Síndrome del Túnel Carpiano , Nervio Mediano , Descompresión Quirúrgica , Disección , Femenino , Mano/anatomía & histología , Humanos , MasculinoRESUMEN
New techniques to stabilize and correct the thoracic and lumbar spine have been developed in recent years. In view of the wide variety and complexity of fixation devices, the optimum configuration of spinal instrumentation systems needs to be defined. Linear and angular measurements of both vertebral pedicles were made in ten complete thoracic and lumbar cadaveric spines using callipers and a goniometer. The vertical interpedicular distance gradually increased along the spine up to L5. The transverse interpedicular distance was larger at both ends of the spine. Pedicular height gradually increased from T1 to L5, plateauing between T3 and T9, being widest at the thoracolumbar junction. Pedicular width was greatest at the three junctional regions of the spine. The sagittal pedicular angle decreased along the length of the spine to zero at L5. The transverse pedicular angle decreased from T1 to T12 and then increased to L5. Of the pedicular measurements only width limits the diameter of fixation screws. The vertical interpedicular distance determines the distance between the holes of plates, while the length of the transfixator is related to the transverse interpedicular distance. The pedicular angles enable triangulation of screws and determine the stability of the fixation.
Asunto(s)
Tornillos Óseos , Vértebras Lumbares/anatomía & histología , Vértebras Torácicas/anatomía & histología , Anciano , Anciano de 80 o más Años , Estatura/fisiología , Cadáver , Diseño de Equipo , Femenino , Humanos , Fijadores Internos , Vértebras Lumbares/fisiología , Masculino , Persona de Mediana Edad , Vértebras Torácicas/fisiologíaRESUMEN
The question remains unanswered regarding the role of repair of medial ligament injuries associated with subluxation of the elbow and non-reconstructable radial head fracture and whether or not this will decrease the risk of chronic instability and cubitus valgus. The goal of this study was to define the role of the medial ligamentous complex of the elbow in elbow instability and to describe the anatomy of the complex in 35 fresh-frozen cadaver elbows. We documented medial ligamentous complex anatomy and compared our results to those in the literature. 25 elbows were dissected in order to describe the different bundles of the medial ligament complex and to precise the positions of the elbow that placed each in tension; section of the different ligamentous bundles was done to study the role of each in elbow stability. 10 other elbows were dissected and used for the ligamentous section studies which were performed subcutaneously. We found two bundles at the level of the anterior portion and termed them superficial and deep. Section of the anterior bundle lead to posterior subluxation of the elbow at 30-100 degrees flexion in both supination and pronation. Posterior subluxation was obtained after an anterior capsulotomy; medial epicondylectomy did not compromise the stability of the elbow after a complete section of the insertion of the deep fibers of the anterior bundle. Elements thus required for stability of the elbow are integrity of the articular surface of the humerus and the ulna, and the anterior bundle of the medial ligamentous complex.
Asunto(s)
Articulación del Codo/anatomía & histología , Inestabilidad de la Articulación/etiología , Ligamentos Articulares/anatomía & histología , Adulto , Anciano , Anciano de 80 o más Años , Cadáver , Disección , Articulación del Codo/fisiología , Femenino , Humanos , Inestabilidad de la Articulación/fisiopatología , Ligamentos Articulares/fisiología , Masculino , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
The central nervous system octapeptide, neuropeptide FF (NPFF), is believed to play a role in pain modulation and opiate tolerance. Two G protein-coupled receptors, NPFF1 and NPFF2, were isolated from human and rat central nervous system tissues. NPFF specifically bound to NPFF1 (K(d) = 1.13 nm) and NPFF2 (K(d) = 0.37 nm), and both receptors were activated by NPFF in a variety of heterologous expression systems. The localization of mRNA and binding sites of these receptors in the dorsal horn of the spinal cord, the lateral hypothalamus, the spinal trigeminal nuclei, and the thalamic nuclei supports a role for NPFF in pain modulation. Among the receptors with the highest amino acid sequence homology to NPFF1 and NPFF2 are members of the orexin, NPY, and cholecystokinin families, which have been implicated in feeding. These similarities together with the finding that BIBP3226, an anorexigenic Y1 receptor ligand, also binds to NPFF1 suggest a potential role for NPFF1 in feeding. The identification of NPFF1 and NPFF2 will help delineate their roles in these and other physiological functions.
Asunto(s)
Arginina/análogos & derivados , Oligopéptidos/metabolismo , Receptores de Superficie Celular/metabolismo , Receptores de Neuropéptido/química , Receptores de Neuropéptido/metabolismo , Secuencia de Aminoácidos , Animales , Arginina/metabolismo , Sitios de Unión , Encéfalo/metabolismo , Células COS , Calcio/metabolismo , Mapeo Cromosómico , Clonación Molecular , AMP Cíclico/metabolismo , ADN Complementario/metabolismo , Electrofisiología , Biblioteca de Genes , Humanos , Cinética , Ligandos , Datos de Secuencia Molecular , Oocitos , Fosfatidilinositoles/metabolismo , Unión Proteica , Estructura Terciaria de Proteína , ARN Mensajero/metabolismo , Ratas , Receptores de Superficie Celular/química , Receptores de Neuropéptido/biosíntesis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia de Aminoácido , Distribución Tisular , XenopusRESUMEN
Two structurally related, G-protein-coupled receptors were identified as receptors for the neuropeptide, neuromedin U. This peptide is found in highest levels in the gut and genitourinary system where it potently contracts smooth muscle but is also expressed in the spinal cord and discrete regions of the brain. Binding sites for neuromedin U have been characterized in rat uterus, however, little is known about the activity of this peptide in the regions of the central nervous system where it is expressed. The receptors characterized in this report are activated by neuromedin U at nanomolar potency in heterologous expression systems and bind radiolabeled neuromedin U with high affinity. Localization of the receptor RNA by quantitative reverse transcription-polymerase chain reaction in a variety of human tissues shows distinct expression patterns for the two receptors. NMU1 is expressed predominantly in peripheral tissues, whereas NMU2 is more highly expressed in the central nervous system. Identification of neuromedin U receptor subtypes will greatly aid in the determination of the physiological roles of this peptide.
Asunto(s)
Encéfalo/metabolismo , Proteínas de la Membrana , Receptores de Neurotransmisores/fisiología , Secuencia de Aminoácidos , Animales , Células COS , Calcio/metabolismo , Clonación Molecular , Secuencia Conservada , Femenino , Humanos , Fosfatos de Inositol/metabolismo , Datos de Secuencia Molecular , Neuropéptidos/farmacología , Oocitos/fisiología , Sistemas de Lectura Abierta , Especificidad de Órganos , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/fisiología , Ensayo de Unión Radioligante , Ratas , Receptores de Neurotransmisores/química , Receptores de Neurotransmisores/genética , Proteínas Recombinantes/metabolismo , Sistemas de Mensajero Secundario/efectos de los fármacos , Sistemas de Mensajero Secundario/fisiología , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Porcinos , Transfección , Xenopus laevisRESUMEN
Cyclohexylamino oxazoline 1 (AGN 190837), an analogue of 2 (Bay a6781), is a potent alpha(2) adrenoceptor agonist. On the basis of a design generated by receptor-ligand modeling, a number of cyclohexyl and norbornyl analogues were synthesized wherein the propyl group of 1 was replaced by phenylalkyl subsituents. This resulted in compound 6 being an alpha(2c) selective agonist, as well as 7 and 9 being alpha(2a)/alpha(2c) selective.
Asunto(s)
Agonistas de Receptores Adrenérgicos alfa 2 , Agonistas alfa-Adrenérgicos/síntesis química , Oxazoles/síntesis química , Agonistas alfa-Adrenérgicos/farmacología , Antihipertensivos/síntesis química , Antihipertensivos/química , Antihipertensivos/farmacología , Clonación Molecular , Humanos , Indicadores y Reactivos , Modelos Moleculares , Método de Montecarlo , Oxazoles/química , Oxazoles/farmacologíaRESUMEN
The penile veins are thought to be responsible for some erectile disorders. The aim of this study was to describe the anatomy and function of these veins. The venous systems of 25 cadaveric penises were studied by various anatomic and histologic techniques. The superficial veins arising from the tegumentary layers drain into the superficial dorsal vein which in three-quarters of cases empties into the left great saphenous vein. The veins of the deep internal system, running below the deep fascia of the penis, emerge from the erectile bodies and can be divided into two systems, one anterosuperior and the other posteroinferior. The anterosuperior system comprises the veins of the glans which will form the deep dorsal vein; the latter receives blood from the medial portion of the corpus spongiosum and from the free portion of the corpora cavernosum mainly via the circumflex veins. It ends in the pre-prostatic plexus. The posteroinferior system, issuing from the posterior portion of the erectile bodies, is composed of the bulbar, cavernous and crural veins which drain towards the pre-prostatic plexus and the internal pudendal veins. Anastomoses link the two networks, superficial and deep. Study of the structure of the veins of the deep system reveals the presence of muscular cushions, which we have shown to have adrenergic innervation. These findings are compared with those of the literature, which show variations which are mainly of number. The place of veins in the mechanism of erection is discussed.
Asunto(s)
Pene/irrigación sanguínea , Vena Safena/anatomía & histología , Adulto , Anciano , Cadáver , Molde por Corrosión , Humanos , Masculino , Erección Peniana/fisiología , Pene/fisiología , Vena Safena/fisiologíaRESUMEN
NPY is a 36-amino acid peptide which exerts its physiological effects through the activation of a family of G-protein coupled receptors. In vivo and in vitro characterization of the recently cloned rat Y5 receptor suggests that it is a primary mediator of NPY-induced feeding (Gerald et al., Nature 1996;382:168-171). We now report the molecular cloning and pharmacological characterization of the human, dog and mouse homologs of the Y5 receptor. With the exception of a 21 amino acid repeat in the amino terminus of the mouse Y5 receptor, the sequence of the four species homologs appear to be highly conserved, with 88% to 97% amino acid identities between any two species. Similarly, the pharmacological profiles of the four species homologs as determined in porcine 125I-PYY binding assays show a great deal of conservation, with the following rank order of affinity: human or porcine NPY, PYY, [Leu31,Pro34]NPY, NPY(2-36), human PP > human [D-Trp32]NPY > rat PP, C2-NPY. Northern blot analysis reveals that the Y5 receptor is widely distributed in the human brain, with the strongest signals detected in the cortex, putamen and caudate nucleus. The chromosomal localization of the human Y5 receptor, previously shown to be overlapping and in the opposite orientation to the Y1 receptor, is determined to be 4q31, the same locus as previously demonstrated for the human Y1 receptor (Herzog et al., J Biol Chem 1993;268:6703-6707), suggesting that these receptors may be coregulated. These Y5 species homologs along with corresponding animal models may be useful in the search for novel therapeutics in the treatment of obesity and related feeding disorders.
Asunto(s)
Receptores de Neuropéptido Y/genética , Receptores de Neuropéptido Y/metabolismo , Secuencia de Aminoácidos , Animales , Células COS , Cromosomas Humanos Par 4/genética , Clonación Molecular , Perros , Humanos , Hibridación Fluorescente in Situ , Cinética , Ratones , Datos de Secuencia Molecular , Neuropéptido Y/metabolismo , Polipéptido Pancreático/metabolismo , Péptido YY/metabolismo , Filogenia , Ratas , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Homología de Secuencia de Aminoácido , Especificidad de la Especie , TransfecciónRESUMEN
The neuropeptide galanin has been implicated in the regulation of processes such as nociception, cognition, feeding behavior, and hormone secretion. Multiple galanin receptors are predicted to mediate its effects, but only two functionally coupled receptors have been reported. We now report the cloning of a third galanin receptor distinct from GALR1 and GALR2. The receptor, termed GALR3, was isolated from a rat hypothalamus cDNA library by both expression and homology cloning approaches. The rat GALR3 receptor cDNA can encode a protein of 370 amino acids with 35% and 52% identity to GALR1 and GALR2, respectively. Localization of mRNA by solution hybridization/RNase protection demonstrates that the GALR3 transcript is widely distributed, but expressed at low abundance, with the highest levels in the hypothalamus and pituitary. We also isolated the gene encoding the human homologue of GALR3. The human GALR3 receptor is 90% identical to rat GALR3 and contains 368 amino acids. Binding of porcine 125I-galanin to stably expressed rat and human GALR3 receptors is saturable (rat KD = 0.98 nM and human KD = 2.23 nM) and displaceable by galanin peptides and analogues in the following rank order: rat galanin, porcine galanin approximately M32, M35 approximately porcine galanin-(-7 to +29), galantide, human galanin > M40, galanin-(1-16) > [D-Trp2]galanin-(1-29), galanin-(3-29). This profile resembles that of the rat GALR1 and GALR2 receptors with the notable exception that human galanin, galanin-(1-16), and M40 show lower affinity at GALR3. In Xenopus oocytes, activation of rat and human GALR3 receptors co-expressed with potassium channel subunits GIRK1 and GIRK4 resulted in inward K+ currents characteristic of Gi/Go-coupled receptors. These data confirm the functional efficacy of GALR3 receptors and further suggest that GALR3 signaling pathways resemble those of GALR1 in that both can activate potassium channels linked to the regulation of neurotransmitter release.
Asunto(s)
Canales de Potasio de Rectificación Interna , Receptores de Neuropéptido/genética , Secuencia de Aminoácidos , Animales , Unión Competitiva , Clonación Molecular , Conductividad Eléctrica , Canales de Potasio Rectificados Internamente Asociados a la Proteína G , Proteínas de Unión al GTP/metabolismo , Galanina/metabolismo , Humanos , Hipotálamo , Datos de Secuencia Molecular , Hipófisis , Canales de Potasio/metabolismo , Unión Proteica , Ratas , Receptores de Galanina , Receptores de Neuropéptido/clasificación , Homología de Secuencia de Aminoácido , Transducción de Señal , Especificidad de la Especie , Distribución TisularRESUMEN
A number of novel dihydropyridine derivatives based upon 1, 4-dihydro-3-(methoxycarbonyl)-2, 6-dimethyl-4-(4-nitrophenyl)-5-((3-(4, 4-diphenylpiperidin-1-yl)propyl)aminocarbonyl)pyridine (4) have been synthesized and tested at cloned human alpha adrenoceptors as well as the rat L-type calcium channel. Within this compound series, 5-(aminocarbonyl)-1,4-dihydro-2, 6-dimethyl-4-(4-nitrophenyl)-3-((3-(4, 4-diphenylpiperidin-1-yl)propyl)aminocarbonyl)pyridine (19) displayed good binding affinity and selectivity for the alpha1a adrenoceptor (pKi = 8.73) and potently inhibited (pA2 = 9.23) phenylephrine-induced contraction of the human prostate.
Asunto(s)
Agonistas alfa-Adrenérgicos/farmacología , Antagonistas Adrenérgicos alfa/farmacología , Fenilefrina/farmacología , Piperidinas , Próstata/efectos de los fármacos , Piridinas , Receptores Adrenérgicos alfa 1/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Canales de Calcio/efectos de los fármacos , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Músculo Liso/fisiopatología , Piperidinas/síntesis química , Piperidinas/metabolismo , Piperidinas/farmacología , Próstata/fisiopatología , Hiperplasia Prostática/fisiopatología , Piridinas/síntesis química , Piridinas/metabolismo , Piridinas/farmacología , RatasRESUMEN
Few studies have been done about the venous vascularization of the spine since neuroradiologic studies in the 1960s and 70s. The aim of this study was to clarify the topography of the internal vertebral venous plexuses in relation to the posterior longitudinal ligament and the dura. The relationships of the vv. were studied at different levels of the spine. The internal vertebral venous system of seven cadavers was injected with a blue bicomponent silicon rubber. It consisted with an anterior and a posterior venous plexus. At the cervical level, the anterior longitudinal vv. are located in a dehiscence of the periosteal layer, in the lateral part of the spinal canal. At each level, they joined the contralateral one at the midline by a retrocorporeal v. located behind the posterior longitudinal ligament. No vv. were found in the epidural space. There was a major development of the retrocorporeal v. of the axis, but it did not receive any venous drainage from the vertebral body. At the thoracic and lumbar levels, the anterior venous plexuses remain within a dehiscence of the periosteal layer, which is thinner. The retrocorporeal vv. become pre-ligamentous. We did not find any posterior venous plexuses at the cervical level, but they were evident at the thoracic level and became more voluminous and sinusoidal in the lumbar region.
Asunto(s)
Columna Vertebral/irrigación sanguínea , Adulto , Cadáver , Humanos , Venas/anatomía & histologíaRESUMEN
We describe a very uncommon case of gastric duplication with heterotopic pancreas suggested by an acute pancreatitis and complicated by pseudocyst formation. Diagnostics, hypothesis and management are discussed.
Asunto(s)
Coristoma/cirugía , Páncreas , Seudoquiste Pancreático/cirugía , Pancreatitis/cirugía , Gastropatías/cirugía , Estómago/anomalías , Enfermedad Aguda , Preescolar , Coristoma/patología , Femenino , Humanos , Páncreas/patología , Seudoquiste Pancreático/patología , Pancreatitis/patología , Estómago/patología , Gastropatías/patologíaRESUMEN
The authors described a method of vascular injection with a coloured silicon rubber. The injected material was a biocomponent silicon elastomer, with ambiant temperature room vulcanizing. It was supple, easily dissequable and diffuse well into all small caliber vessels. The soft pressure injection did not cause neither material collection by vessels rupture nor anatomic structure distortion. This material could constitute an excellent alternative to coloured latex injection.
Asunto(s)
Anatomía/métodos , Calor , Elastómeros de Silicona , Arterias/anatomía & histología , Humanos , Inyecciones Intraarteriales , Inyecciones Intravenosas , Venas/anatomía & histologíaRESUMEN
Neuropeptide Y (NPY) receptors belong to the G-protein-coupled receptor (GPCR) superfamily and mediate several physiological responses, such as blood pressure, food intake, sedation and memory retention. To understand the interactions between the NPY Y1 receptor subtype and its ligands, computer modeling was applied to the natural peptide agonist, NPY and a small molecule antagonist, BIBP3226. An agonist and antagonist binding domain was elucidated using mutagenesis data for the Y1 receptor as well as for other GPCR families. The agonist and antagonist ligands which were investigated appear to share common residues for their interaction within the transmembrane regions of the Y1 receptor structure, including Gln120, Asn283 and His306. This is in contrast to findings with tachykinin receptors where the binding domains of the non-peptide antagonists have very little in common with the binding domains of the agonist, substance-P. In addition, a hydrogen bond between the hydroxyl group of Tyr36 of NPY and the side chain of Gln219, an interaction that is absent in the model complex between Y1 and the antagonist BIBP3226, is proposed as one of the potential interactions necessary for receptor activation.
Asunto(s)
Proteínas de Unión al GTP/química , Modelos Moleculares , Receptores de Neuropéptido Y/química , Secuencia de Aminoácidos , Animales , Arginina/análogos & derivados , Arginina/química , Sitios de Unión , Bovinos , Simulación por Computador , Humanos , Ligandos , Datos de Secuencia Molecular , Estructura Molecular , Mutagénesis Sitio-Dirigida , Neuropéptido Y/química , Neuropéptido Y/genética , Neuropéptido Y/metabolismo , Conformación Proteica , Ingeniería de Proteínas , Receptores de Neuropéptido Y/genética , Receptores de Neuropéptido Y/metabolismoRESUMEN
We cloned and expressed the rat Y4 receptor for pancreatic polypeptide (PP). Structure-activity profiles derived from 125I-PP binding assays and [cAMP] radioimmunoassays reveal a selective receptor interaction with rat PP vs. neuropeptide Y (NPY) or peptide YY (PYY). Rat and human Y4 receptor clones share 75% amino acid identity. Based on [cAMP] radioimmunoassay, the human Y4 receptor exhibits a less selective interaction with rat PP vs. NPY or PYY and a greater dependence on N-terminal PP residues, relative to rat Y4. Differences in sequence and structure-activity profiles suggest the rat be used with caution to model human Y4 receptor function.