Histamine receptors in the guinea-pig duodenum

Abstract

Guinea‐pig duodenum contracted by histamine or by acetylcholine was relaxed dose‐dependently by a series of H2‐receptor selective agonists namely dimaprit, impromidine, clonidine and tolazoline. This relaxation was not neurally mediated since it was not modified by tetrodotoxin nor was it exerted through sympathetic receptors because it was not modified by pretreatment with propranolol or phentolamine. Apparently it was connected with the H2‐receptor stimulation more than to peculiarities of the single compounds. However a series of H2‐blockers (metiamide, cimetidine, ranitidine or oxmetidine) were unable to counteract the effect of the H2‐agonists or the relaxant effect of histamine in the presence of chlorpheniramine. This peculiar situation seems to indicate the existence of anomalous H2‐receptors, susceptible to the action of the agonists but not to that of the antagonists.

Evidence against the temperature‐dependent interconversion of histamine H1‐ and H2‐receptors in the guinea‐pig ileum

“…On the other hand H2-receptor agonists, dimaprit and impromidine were always devoid of stimulatory effects up to concentrations higher than 30 jLg/ml. They exerted a relaxant effect on the contraction elicited by histamine at 12°C having the same behaviour at 37°C and thus confirming our previous results obtained in the guinea-pig duodenum (Bertaccini & Zappia, 1981). Moreover, cimetidine was ineffective at 12°C exactly as it was at 37°C again confirming some previous observations (Bertaccini, Molina, Zappia & Sz6li, 1979).…”

Effects of histamine H1‐, H2‐ and H3‐receptor selective drugs on the mechanical activity of guinea‐pig small and large intestine

“…H2-receptor agonists, like dimaprit, impromidine and clonidine (also an a2-agonist), caused relaxations with a potency lower than that usually found for e.g. the positive chronotropic effect on guinea-pig right atrium (Bertaccini & Zappia, 1981). The relaxations could however not be inhibited by the H2-antagonists metiamide, cimetidine, ranitidine or oxmetidine, nor by tetrodotoxin, propranolol or phentolamine (Bertaccini & Zappia, 1981).…”

“…the positive chronotropic effect on guinea-pig right atrium (Bertaccini & Zappia, 1981). The relaxations could however not be inhibited by the H2-antagonists metiamide, cimetidine, ranitidine or oxmetidine, nor by tetrodotoxin, propranolol or phentolamine (Bertaccini & Zappia, 1981). Moreover, Fjalland (1979) also suggested the existence of an H2-receptor subtype in guineapig ileum because histamine was shown to suppress electrically-induced twitches of ileal smooth muscle, although the order of potency of H2-antagonists in inhibiting this action of histamine did not correlate with the known activity of the compounds at the H2-receptor of guinea-pig right atrium (Fjalland, 1979).…”

“…Moreover, using selective H2-receptor agents Barker & Ebersole (1982) reported the presence of H2-receptors on guinea-pig myenteric plexus neurones, mediating the release of acetylcholine. To complicate the situation even more, Bertaccini & Zappia (1981) described the presence of an H2-receptor subtype on guinea-pig duodenum, mediating relaxations of precontracted muscle. H2-receptor agonists, like dimaprit, impromidine and clonidine (also an a2-agonist), caused relaxations with a potency lower than that usually found for e.g.…”

“…In the present study we examined several of the problems outlined above, using highly selective histamine receptor agonists and antagonists. In both small and large intestine of the guinea-pig we investigated the possible indirect contractile effects of histamine (Rubenstein & Cohen, 1985), the existence of an H2-receptor subtype, possibly mediating relaxations (Bertaccini & Zappia, 1981), and the inhibition of electricallyinduced twitches of the intestinal smooth muscle in the presence of atropine, as originally described by .…”