Histamine receptors in esophageal smooth muscle of the opossum

Esophageal smooth muscle was examined for histamine receptors. The effects of histamine, the histamine analogs 4-methylhistamine (4-MH) and 2-(2-pyridyl) ethylamine (PEA), the histamine receptor antagonists mepyramine and metiamide, and the histamine-releasing substance compound 48/80, on lower esophageal sphincter (LES) and esophageal body (EB) smooth muscle of the opossum were studied in a superfused tissue bath. Histamine, PEA, an H1 receptor agonist, and compound 48/80 caused a dose-related increase in LES basal tension and in EB off response amplitude, the threshold for histamine being 6.7 X 10(-8) M and that for PEA being 6.7 X 10(-7) M. In the presence of mepyramine, and H1 receptor antagonist, the effects of histamine and compound 48/80 were reversed to inhibition of both LES basal tension and EB off response amplitude, while the effect of PEA was abolished. Metiamide, an H2 receptor antagonist, did not alter responses to histamine, PEA, or compound 48/80. The H2 receptor agonist 4-methylhistamine caused a reduction of LES tension and EB off response amplitude, but caused an increase in those parameters in the presence of metiamide. A combination of mepyramine and metiamide abolished responses to all agonist drugs. The results indicate that LES and EB smooth muscle contain both excitatory H1 and inhibitory H2 receptors for histamine. Endogenous histamine released from storage sites in LES and EB and exogenous histamine both preferentially activate H1 receptors.