title: Histamine receptors in the myenteric plexus-longitudinal muscle of the guinea-pig ileum: H1- and H2-receptor-mediated potentiation of the contractile response to electrical stimulation.
abstract: The effect of histamine on the contractile response to low frequency-electrical field stimulation in the myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum was investigated. By blocking the direct increase in smooth muscle tone caused by histamine with low concentrations of pyrilamine (10(-9)--5 x 10(-8) M) a dose-dependent, histamine-induced potentiation of the twitch response to electrical stimulation was observed. Blocking the direct actions of histamine with concentrations of pyrilamine greater than 10(-7) M resulted in a biphasic histamine dose-response curve: lower histamine concentrations produced a dose-dependent decrease of the twitch response; higher concentrations produced a potentiation. The potentiating effect of histamine was inhibited by high concentrations of H2-receptor antagonists. Tiotidine (ICI 125, 211) had a pA2 of 5.25, 100 times greater than its pA2 in isolated guinea-pig atria. Blockade of the actions of the H2-receptor agonists dimaprit and tetrahydrozoline also required greater antagonist concentrations. The selective H1-receptor agonist, 2-(2-thiazolyl)-ethylamine, also enhanced the response to electrical stimulation. The potentiating effect of histamine could be blocked by hexamethonium (10(-7)--10(-5) M) but not by atropine. Atropine (10(-9)--10(-8) M) did prevent the decrease in the contraction amplitude induced by histamine in the presence of 10(-7) M pyrilamine. The purinergic antagonist theophylline, adrenergic antagonists or depletion of endogenous catecholamines were without effect. Tetrodotoxin (10(-6) M) inhibited the augmentation induced by histamine. Our results demonstrate that histamine potentiates the acetylcholine-mediated contractile response to electrical field stimulation of guniea-pig ileum via H1- and what may be an H2-receptor subtype.
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D007082:Ileum / Q000502:physiology; D066298:In Vitro Techniques; D007422:Intestines / Q000502:physiology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology; D009197:Myenteric Plexus / Q000502:physiology*; D011968:Receptors, Histamine / Q000502:physiology*; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000502:physiology; D011970:Receptors, Histamine H2 / Q000187:drug effects / Q000502:physiology
chemical_list: D006584:Hexamethonium Compounds; D011968:Receptors, Histamine; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D018738:Hexamethonium; D001285:Atropine; D006632:Histamine