title: [Intracellular mechanism of potentiating interaction of histaminergic and muscarinic receptors in rabbit parietal cells].
abstract: Intracellular mechanisms of receptor-mediated acid secretion and potentiating interactions of receptors were explored in isolated gastric glands obtained from the stomach of New Zealand White rabbits. Intracellular free calcium concentration ([Ca2+]i) was measured by a digitized video-image analysis with a dual-wavelength excitation microspectrofluorometry in fura-2 loaded parietal cells, and acid secretion was determined in parallel experiments by monitoring the accumulation of [14C] aminopyrine (AP) in suspension of isolated glands. Histamine and carbachol stimulated acid secretion and increased [Ca2+]i in a concentration-dependent manner. The concentration-response curve for the acid producing effect of carbachol was overlapped by that for the [Ca2+]i-increasing effect. However, the concentration-response curve for the [Ca2+]i-increasing effect of histamine was shifted by approximately one order from that for the acid-producing effect, indicating that a low concentration of histamine can also stimulate acid secretion without [Ca2+]i increase in the rabbit parietal cells. Cimetidine, a H2-blocker, inhibited the histamine-induced acid secretion and [Ca2+]i increase competitively, and those responses induced by carbachol non-competitively. Carbachol at a concentration of 10(-3)M did not affect the histamine concentration of solution containing isolated gastric glands. Neither 10(-6)M 3-isobutyl-1-methyl-xanthine (IBMX) nor 3 x 10(-5)M dibutyryl adenosine 3',5'-cyclic monophosphate (dbcAMP) affected AP uptake and [Ca2+]i per se. However, these agents significantly potentiated the carbachol-induced acid secretion and [Ca2+]i increase. These results suggest that tonic stimulation of H2-receptors by a small amount of endogenous histamine potentiates the cholinergic acid secretion and [Ca2+]i increase. Parietal cells preconditioned by a small increase in intracellular cAMP may easily increase [Ca2+]i and acid secretion in response to cholinergic stimulation.
authors.affiliation: Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Oikawa
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D004357:Drug Synergism; D005744:Gastric Acid / Q000378:metabolism; D006632:Histamine / Q000032:analysis / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D010295:Parietal Cells, Gastric / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D011968:Receptors, Histamine / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects*
chemical_list: D011968:Receptors, Histamine; D011976:Receptors, Muscarinic; D002927:Cimetidine; D006632:Histamine; D002217:Carbachol; D002118:Calcium