RESUMEN
Marijuana has been used by humans for thousands of years for both medicinal and recreational purposes. This included the treatment of pain, inflammation, seizures, and nausea. In the 1960s, the structure of the principal psychoactive ingredient Δ9-tetrahydrocannabinol was determined, and over the next few decades, two cannabinoid receptors were characterized along with the human endocannabinoid system and what it affects. This includes metabolism, the cardiovascular and reproductive systems, and it is involved in such conditions as inflammation, cancer, glaucoma, and liver and musculoskeletal disorders. In the central nervous system, the endocannabinoid system has been linked to appetite, learning, memory, and conditions such as depression, anxiety, schizophrenia, stroke, multiple sclerosis, neurodegeneration, addiction, and epilepsy. It was the profound effectiveness of cannabidiol, a non-psychoactive ingredient of marijuana, to relieve the symptoms of Dravet syndrome, a severe form of childhood epilepsy, that recently helped spur marijuana research. This has helped substantially to change society's attitude towards this potential source of useful drugs. However, research has also revealed that the actions of endocannabinoids, such as anandamide and 2-arachidonoylglycerol, and the phytocannabinoids, tetrahydrocannabinol and cannabidiol, were not just due to interactions with the two cannabinoid receptors but by acting directly on many other targets including various G-protein receptors and cation channels, such as the transient receptor potential channels for example. This mini-review attempts to survey the effects of these 4 important cannabinoids on these currently identified targets.
RESUMEN
Ever since the late-eighties when endothelium-derived relaxing factor was found to be the gas nitric oxide, endogenous nitric oxide production has been observed in virtually all animal groups tested and additionally in plants, diatoms, slime molds and bacteria. The fact that this new messenger was actually a gas and therefore didn't obey the established rules of neurotransmission made it even more intriguing. In just 30 years there is now too much information for useful comprehensive reviews even if limited to animals alone. Therefore this review attempts to survey the actions of nitric oxide on development and neuronal function in selected major invertebrate models only so allowing some detailed discussion but still covering most of the primary references. Invertebrate model systems have some very useful advantages over more expensive and demanding animal models such as large, easily identifiable neurons and simple circuits in tissues that are typically far easier to keep viable. A table summarizing this information along with the major relevant references has been included for convenience.
RESUMEN
Cannabinoid hyperemesis is a relatively rare but significant adverse effect of chronic marijuana use characterized by severe, cyclic nausea, vomiting, and abdominal pain and marked by compulsive hot-water bathing for temporary symptom relief. A 37-year-old African American male with no significant medical history other than the habitual abuse of marijuana was admitted for intractable nausea, vomiting, and abdominal pain. With the exception of abdominal skin hyperpigmentation and scarring secondary to the direct application of heat through a heating pad, physical examination of the abdomen was unremarkable. Laboratory studies revealed a mild leukocytosis and acute renal dysfunction. All diagnostic examinations were found to be unremarkable or noncontributory to the patient's presenting state. Consistent with previous admissions, the patient's urine toxicology screening was found to be positive for marijuana. After several days of aggressive IV fluid hydration and as needed antiemetics and pain management, all laboratory studies and vital signs returned to baseline and the patient was subsequently discharged. Symptoms of cannabinoid hyperemesis resolve with cannabis cessation and recur when cannabis use is reinitiated, supporting an association between chronic use and cyclic vomiting. A Naranjo algorithm score of 5 revealed a probable incidence of cyclic vomiting associated with chronic cannabis abuse in our patient. Marijuana use, both legal and illegal, is becoming more prevalent in the United States. Given the nationwide increase in marijuana use for recreational and medical reasons, pharmacists and other health care providers should be aware of this interesting drug-induced phenomenon.
Asunto(s)
Dolor Abdominal/inducido químicamente , Abuso de Marihuana/complicaciones , Náusea/inducido químicamente , Vómitos/inducido químicamente , Adulto , Dronabinol/toxicidad , Femenino , Humanos , Masculino , Embarazo , Receptor Cannabinoide CB1/fisiología , SíndromeRESUMEN
OBJECTIVE: To design and assess a horizontally integrated biological sciences course sequence and to determine its effectiveness in imparting the foundational science knowledge necessary to successfully progress through the pharmacy school curriculum and produce competent pharmacy school graduates. DESIGN: A 2-semester course sequence integrated principles from several basic science disciplines: biochemistry, molecular biology, cellular biology, anatomy, physiology, and pathophysiology. Each is a 5-credit course taught 5 days per week, with 50-minute class periods. ASSESSMENT: Achievement of outcomes was determined with course examinations, student lecture, and an annual skills mastery assessment. The North American Pharmacist Licensure Examination (NAPLEX) results were used as an indicator of competency to practice pharmacy. CONCLUSION: Students achieved course objectives and program level outcomes. The biological sciences integrated course sequence was successful in providing students with foundational basic science knowledge required to progress through the pharmacy program and to pass the NAPLEX. The percentage of the school's students who passed the NAPLEX was not statistically different from the national percentage.
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Disciplinas de las Ciencias Biológicas/educación , Curriculum , Educación en Farmacia/métodos , Evaluación Educacional/métodos , Facultades de Farmacia , Estudiantes de Farmacia , Disciplinas de las Ciencias Biológicas/normas , Competencia Clínica/normas , Curriculum/normas , Educación en Farmacia/normas , Evaluación Educacional/normas , Humanos , Facultades de Farmacia/normasRESUMEN
The generation of the novel messenger molecule nitric oxide (NO) has been demonstrated in many tissues across phyla including nervous systems. It is produced on demand by the enzyme nitric oxide synthase often stimulated by intracellular calcium and typically affecting guanylate cyclase thought to be its principal target in an auto and/or paracrine fashion. This results in the generation of the secondary messenger cyclic guanosine monophosphate (cGMP). Nitric oxide synthase has been demonstrated in various mollusk brains and manipulation of NO levels has been shown to affect behavior in mollusks. Apart from modulation of the effect of the peptide GSPYFVamide, there appears little published on direct or modulatory effects of NO on Helix aspersa central neurons. We present here initial results to show that NO can be generated in the region around F1 in the right parietal ganglion and that NO and cGMP directly hyperpolarize this neuron. For example, application of the NO-donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP; 200 µM) can cause a mean hyperpolarization of 41.7 mV, while 2 mM 8-bromo-cyclic guanosine monophosphate (8-bromo-cGMP) produced a mean hyperpolarization of 33.4 mV. Additionally, pre-exposure to NO-donors or cGMP appears to significantly reduce or even eliminates the normal hyperpolarizing K(+)-mediated response to dopamine (DA) by this neuron; 200 µM SNAP abolishes a standard response to 0.5 µM DA while 1 mM 8-bromo-cGMP reduces it 62%.
Asunto(s)
Caracoles Helix/efectos de los fármacos , Óxido Nítrico/farmacología , Acetilcolina/farmacología , Animales , Calcio/metabolismo , GMP Cíclico/análogos & derivados , GMP Cíclico/farmacología , Dopamina/farmacología , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Caracoles Helix/anatomía & histología , Potenciales de la Membrana/efectos de los fármacos , NG-Nitroarginina Metil Éster/farmacología , Sistema Nervioso/citología , Neuronas/efectos de los fármacos , Neurotransmisores/farmacología , Donantes de Óxido Nítrico/farmacología , Nitroprusiato/farmacología , Técnicas de Placa-Clamp , S-Nitroso-N-Acetilpenicilamina/farmacologíaRESUMEN
Drosophila melanogaster behavioral mutants have been isolated in which the ability to form associative olfactory memories has been disrupted primarily by altering cyclic adenosine monophosphate signal transduction. Unfortunately, the small size of the fruit fly and its neurons has made the application of neurobiological techniques typically used to investigate the physiology underlying these behaviors daunting. However, the realization that adult fruit flies could tolerate a window in the head capsule allowing access to the central structures thought to be involved plus the development of genetically expressed reporters of neuronal function has allowed a meteoric expansion of this field over the last decade. This review attempts to summarize the evolution of the techniques involved from the first use of a window to access these brain areas thought to be involved in associative olfactory learning and memory, the mushroom bodies and antennal lobes, to the current refinements which allow both high-resolution multiphoton imaging and patch clamping of identified neurons while applying the stimuli used in the behavioral protocols. This area of research now appears poised to reveal some very exciting mechanisms underlying behavior.
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Drosophila melanogaster/fisiología , Electrofisiología/historia , Aprendizaje/fisiología , Memoria/fisiología , Animales , Electrofisiología/métodos , Historia del Siglo XX , Historia del Siglo XXI , Cuerpos Pedunculados/fisiología , Percepción OlfatoriaRESUMEN
Olfactory sensory information in Drosophila is transmitted through antennal lobe projections to Mushroom Body neurons (Kenyon cells) by means of cholinergic synapses. Application of acetylcholine (ACh) and odors produce significant increases in intracellular calcium ([Ca(2+)](i)) in these neurons. Behavioral studies show that Kenyon cell activity is modulated by dopaminergic inputs and this modulation is thought to be the basis for an olfactory conditioned response. However, quantitative assessment of the synaptic inputs to Kenyon cells is currently lacking. To assess neuronal activity under in vivo conditions, we have used the endogenously-expressed camgaroo reporter to measure [Ca(2+)](i) in these neurons. We report here the dose-response relationship of Kenyon cells for ACh and dopamine (DA). Importantly, we also show that simultaneous application of ACh and DA results in a significant decrease in the response to ACh alone. In addition, we show inhibition of the ACh response by cyclic adenosine monophosphate. This is the first quantitative assessment of the effects of these two important transmitters in this system, and it provides an important basis for future analysis of the cellular mechanisms of this well established model for associative olfactory learning.
Asunto(s)
Acetilcolina/metabolismo , Dopamina/metabolismo , Drosophila/metabolismo , Cuerpos Pedunculados/metabolismo , Acetilcolina/farmacología , Análisis de Varianza , Animales , Calcio/metabolismo , Dopamina/farmacología , Relación Dosis-Respuesta a Droga , Drosophila/efectos de los fármacos , Drosophila/fisiología , Iontoforesis , Cuerpos Pedunculados/efectos de los fármacos , Cuerpos Pedunculados/fisiología , Vías Olfatorias/metabolismo , Vías Olfatorias/fisiología , Percepción Olfatoria , Procesamiento de Señales Asistido por Computador , Sinapsis/efectos de los fármacos , Sinapsis/metabolismo , Sinapsis/fisiología , Transmisión Sináptica/fisiologíaRESUMEN
Drosophila melanogaster, an established model for genetic manipulation, has recently been used for studying olfactory perception, learning, and memory. Some of these important behavioral phenomena have been dissected with defined mutants, some to a single biochemical lesion, expressed in central brain structures known as the mushroom bodies. A previously introduced preparation used a window in the head capsule through which these structures could be imaged using genetically expressed fluorescent calcium sensors while applying physiological odorant stimuli. Unfortunately, technical constraints prevented direct manipulation of the mushroom bodies with this preparation. I describe here a preparation that will allow, for the first time, the direct pharmacological manipulation of these important structures during imaging in the living adult fly. Responses to discreet applications of acetylcholine were reversibly blocked with tubocurare and reversibly eliminated in calcium-free Ringers. This new technique will significantly enhance the usefulness of the Drosophila model system, allowing a more quantitative examination of the mechanisms involved in olfactory learning and memory.