Pharmacological characterization of histamine H3 receptors in isolated rabbit gastric glands.
The effects of the specific H3 agonist (R)-alpha-methylhistamine (alpha-MeHA) and the specific H3 antagonist thioperamide were examined on histamine release and acid secretion [( 14C]-aminopyrine (AP) accumulation) by isolated rabbit gastric glands. Thioperamide significantly enhanced basal histamine release from the glands (+50% at 30 min for 10(-7) M thioperamide; P less than 0.01), and this increase was prevented by alpha-MeHA. Histamine-elicited AP accumulation was increased by 18% (P less than 0.05) by 10(-7) M thioperamide and decreased by 70% (P less than 0.01) by 10(-6) M of the H2 antagonist ranitidine. Thioperamide alone significantly enhanced AP accumulation in a dose-dependent manner, whereas alpha-MeHA had no effect of its own on this accumulation. Thioperamide stimulation of basal AP accumulation was not modified by ranitidine but was 50% decreased by alpha-MeHA. Furthermore, carbachol-induced AP accumulation was decreased by alpha-MeHA and increased by thioperamide; the latter effect was not blocked by ranitidine. These findings support that H3 receptors pharmacologically distinct from H2 receptors are involved in the regulation of histamine-stimulated acid secretion. They further suggest that these gastric H3 receptors occur in the gastric glands as 1) H3 autoreceptors located on the histamine-secreting cells and acting to downregulate histamine release from these cells and 2) H3 (or H3-like) receptors located on the parietal cell and regulating in a negative manner the acid secretory process.
Institut National de la Santé et de la Recherche Médicale, Unité 10, Hôpital Bichat, Paris, France.
A
A
Bado
L
L
Moizo
J P
JP
Laigneau
M J
MJ
Lewin
D000632:Aminopyrine / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D005753:Gastric Mucosa / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011817:Rabbits; D011899:Ranitidine / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000378:metabolism*
D008761:Methylhistamines; D010880:Piperidines; D011969:Receptors, Histamine H1; D000632:Aminopyrine; C069357:alpha-methylhistamine; D006632:Histamine; D011899:Ranitidine; D002217:Carbachol; C052075:thioperamide