Beta-adrenergic and prostanoid inhibition of canine fundic mucosal mast cells.
We examined regulation of histamine release from canine hepatic and fundic mucosal mast cells in short-term culture. We found that beta- but not alpha-adrenergic agonists markedly inhibited concanavalin A (ConA)-stimulated histamine release. Inhibition by epinephrine was reversed by the beta-antagonist propranolol, but not by the alpha-adrenergic antagonists phentolamine or yohimbine. The beta 2-selective antagonist ICI 115881 reversed the effects of epinephrine, whereas the beta 1-antagonists practolol and betaxolol had little effect. Prostaglandin E2 (PGE2), but not its analogue enprostil, inhibited ConA-stimulated histamine release. This difference may relate to the ability of PGE2, but not enprostil, to stimulate adenosine 3',5'-cyclic monophosphate (cAMP) production. Forskolin, cAMP analogues, and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine also effectively inhibited ConA-stimulated histamine release. Neither adrenergic agonists nor PGE2 inhibited histamine release stimulated by the combination of phorbol 12-myristate-13-acetate plus the calcium ionophore A23187. These data suggest that inhibition was mediated via cAMP-dependent mechanisms and was exerted on primary cell activation, rather than on postreceptor activating events.
Soll
A H
AH
Center for Ulcer Research and Education, Veterans Administration Wadsworth Hospital Center, Los Angeles, California.
Toomey
M
M
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D015232:Dinoprostone / Q000494:pharmacology*; D004285:Dogs; D016620:Enprostil; D004837:Epinephrine / Q000494:pharmacology; D005748:Gastric Fundus / Q000166:cytology; D005753:Gastric Mucosa / Q000166:cytology*; D006636:Histamine Release / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D008099:Liver / Q000166:cytology; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011459:Prostaglandins E, Synthetic; D003208:Concanavalin A; D005576:Colforsin; D000001:Calcimycin; C026777:ICI 118551; D011433:Propranolol; D000242:Cyclic AMP; D016620:Enprostil; D015232:Dinoprostone; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine; D004837:Epinephrine