RESUMEN
N,N-Diethyl-2-(1-pyridyl)-ethylamine (E-2-P) has been shown previously to behave as a simple partial agonist at the histamine H1-receptor of guinea-pig ileum. When isolated longitudinal muscle strips from this preparation were tested with E-2-P before and after blockade with 2-haloalkylamines, it was found that these agents produced an irreversible shift to the right in the dose-response curve without significant depression of the maximum response even at very high antagonist concentrations. Under these circumstances the maximum response to the partial agonist may exceed the maximum response to histamine itself since the latter shows a much diminished maximum response at a very high concentrations of antagonist. These findings are not readily explicable in terms the usual "receptor-reserve' model of the histamine receptor system in ileum. A tentative explanation is provided, involving interaction with the antagonist at more than one site.
Asunto(s)
Etilaminas/antagonistas & inhibidores , Receptores Histamínicos H1/efectos de los fármacos , Receptores Histamínicos/efectos de los fármacos , Animales , Dibencilcloretamina/farmacología , Etilaminas/farmacología , Cobayas , Histamina/farmacología , Técnicas In Vitro , Contracción Muscular/efectos de los fármacos , Fenoxibenzamina/farmacologíaRESUMEN
The effects of histamine on spiral strips of rabbit renal artery have been recorded. Histamine causes dose-dependent contractions of this preparation which are not antagonized by the H2 receptor blocking agent metiamide, but which are blocked by the H1 antagonist diphenhydramine. The pA(2) for the latter agent is similar to that observed at 37 degrees C in intestinal smooth muscle. No evidence of a relaxant population of H2 receptors was encountered. Unlike that of intestinal smooth muscle, the response of strips of renal artery becomes progressively diminished at temperatures below about 20 degrees C, and the effect of reduced temperature on receptor subtype is thus more difficult to assess. It appears, however, that there is no change in type from the H1 receptor observed at 37 degrees C and thus the temperature-dependent transformation which has been reported previously does not occur in all H1 systems.
