RESUMEN
Substance P is an undecapeptide found in multiple sites throughout the central and peripheral nervous systems including small unmyelinated (type C) cutaneous nerve fibers. Previous studies demonstrated that antidromic stimulation results in substance P (SP) release from nerve endings, SP stimulates histamine release (HR) from rat mast cells in vitro, and intradermal SP in humans produces wheals identical to those induced by histamine. These studies suggest a possible role for SP as a link between neurologic events and cutaneous mast cell-mediated reactions. We therefore investigated SP-induced HR in an in vitro preparation of human skin mast cells. Human foreskin sections were incubated with varying concentrations of SP. Histamine was assayed using automated fluorimetry and release was calculated as a percentage of total tissue histamine. Substance P caused dose-dependent HR over a range from 10(-5) M (1.3%) to 5 X 10(-4) M (25.1%). Histamine release was optimal at 3 mM calcium and was blocked by pretreatment with calcium chelation. Naloxone failed to block HR. These studies suggest that HR from skin mast cells by SP may play a role in neural modulation of poorly understood inflammatory skin conditions.
Asunto(s)
Histamina/metabolismo , Mastocitos/metabolismo , Piel/metabolismo , Sustancia P/farmacología , Calcio/farmacología , Relación Dosis-Respuesta a Droga , Humanos , Recién Nacido , Masculino , Naloxona/farmacología , Concentración Osmolar , Piel/citología , Factores de TiempoRESUMEN
Intravenous administration of morphine sulfate often produces urticarial and hypotensive reactions associated with elevations in plasma histamine. The source of this histamine and mechanisms controlling its release are poorly understood. Previous studies of morphine-induced histamine release compared human leukocytes to rat peritoneal mast cells. The effects of morphine on human cutaneous mast cells has not been examined. We studied in vitro histamine release from human basophils and human skin preparations containing cutaneous mast cells to evaluate their relative contribution to the pharmacologic effects of morphine. Human skin mast cell preparations showed dose-dependent histamine release over a morphine concentration range of 1.5 X 10(-5) to 4.5 X 10(-3) M, with peak release occurring at 5 X 10(-4) M, with peak release occurring at 5 X 10(-4) M. Clinically, morphine sulfate is usually injected as a 1.5 X 10(-2) M solution. Histamine release was calcium dependent and equivalent to that obtained with 3 and 10 mM strontium. Morphologic examination revealed degranulation and exocytosis occurring in morphine-stimulated tissue but not in specimens exposed to buffer alone. Lactate dehydrogenase levels did not increase following morphine incubation, thus supporting a noncytolytic mechanism of histamine release. Basophils, in contrast, showed no significant histamine release from exposure to morphine up to 10(-2) M. Concanavalin A, as a positive control in these same preparations, produced a mean histamine release of 21.0%.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Basófilos/fisiología , Liberación de Histamina/efectos de los fármacos , Mastocitos/fisiología , Morfina/farmacología , Basófilos/efectos de los fármacos , Calcio/farmacología , Femenino , Sangre Fetal , Humanos , Técnicas In Vitro , Recién Nacido , L-Lactato Deshidrogenasa/metabolismo , Leucocitos/citología , Leucocitos/fisiología , Masculino , Mastocitos/efectos de los fármacos , Embarazo , Piel/efectos de los fármacos , Fenómenos Fisiológicos de la Piel , Estroncio/farmacologíaRESUMEN
A 29 year-old female patient suffered vascular collapse which became apparent immediately after general anaesthesia. Resuscitation was prolonged and difficult, and complicated by the need for reoperation. Based on the time history, fentanyl was suspected as the causative agent. Fentanyl allergy was confirmed by skin testing one month later. The case is discussed, and the possible reasons for the delay in appearance of symptoms and signs are considered.
Asunto(s)
Analgésicos/efectos adversos , Anafilaxia/inducido químicamente , Fentanilo/efectos adversos , Pruebas Intradérmicas , Pruebas Cutáneas , Adulto , Anestesia General , Femenino , Humanos , Riesgo , Tolmetina/efectos adversos , Tolmetina/análogos & derivadosRESUMEN
Human skin mast cell preparations were incubated with thiopental, thiamylal, methohexital, and pentobarbital in concentrations ranging from 10(-5) M to 10(-3) M. Both thiopental- and thiamylal-induced dose-related histamine release, with thiamylal having a significantly greater effect than thiopental (P less than 0.05). In contrast, incubation of skin mast cell preparations with the same concentrations of pentobarbital and methohexital failed to increase histamine release above spontaneous levels at any concentration. The release of histamine by thiopental and thiamylal was not accompanied by the leakage of lactic dehydrogenase (LDH). Although a demonstration of histamine release in vitro is not proof that clinical symptoms are causally related to histamine release in vivo, methohexital may be preferred as the induction agent in patients showing extreme sensitivity to histamine (asthmatics) or increased histamine releasability (atopics).
Asunto(s)
Anestésicos/farmacología , Liberación de Histamina/efectos de los fármacos , Mastocitos/metabolismo , Tiobarbitúricos/farmacología , Humanos , Técnicas In Vitro , L-Lactato Deshidrogenasa/metabolismo , Mastocitos/efectos de los fármacos , Mastocitos/enzimología , Metohexital/farmacología , Pentobarbital/farmacología , Piel/efectos de los fármacos , Piel/enzimología , Piel/metabolismo , Tiamilal/farmacología , Tiopental/farmacologíaRESUMEN
Human leukocyte and skin mast cell preparations were incubated with morphine sulfate in concentrations ranging from 1.5 X 10(-5) M to 4.5 X 10(-3) M. Skin mast cells also were incubated with oxymorphone and fentanyl in the same concentrations. Human leukocytes did not release histamine in response to any concentration of morphine. In skin mast cells, histamine release by morphine first was detected at 1.5 X 10(-4) M. Histamine release further increased at 5.0 X 10(-4) M with no incremental increase at higher concentrations. Oxymorphone and fentanyl failed to release histamine at any concentration. Histamine release by morphine required calcium but was not influenced by changes in the 1-4 mM range. Skin mast cell preparations were pretreated for 30 min in naloxone 5 X 10(-4) M and then morphine 5 X 10(-4) M was added for 30 min without removing naloxone. Naloxone neither released histamine nor inhibited morphine-induced histamine release. The release of histamine by morphine but not equimolar concentrations of fentanyl and oxymorphone indicates that histamine release by narcotics is not a nonspecific effect of high drug concentration. The failure of naloxone to inhibit morphine-induced histamine release suggests that histamine release by morphine is not dependent on opiate receptor binding or activation. These results indicate that this human mast cell preparation will be useful in further understanding the mechanism of histamine release induced by morphine and other agents.