Effect of epinephrine on cAMP generation in transfected Hepa cells
(a) Epinephrine dose-dependently stimulated cAMP generation in nontransfected Hepa cells (EC50 = 5 × 10−8 M, maximum response = 278 ± 44% above control, means ± SEM, n = 4). This effect was inhibited by propranolol (10−5 M) but not by cimetidine (10−5 M). In Hepa cells transfected with the wild-type H2 receptor (b), epinephrine stimulated cAMP generation in a biphasic fashion. The stimulatory effect of low-dose epinephrine (10−11 to 10−9 M) on cAMP formation was inhibited by cimetidine and not by propranolol, while the effect observed with higher concentrations of epinephrine (10−8 to 10−4 M) was inhibited by propranolol and not by cimetidine. (c) The stimulatory action of epinephrine on cAMP generation was markedly enhanced in Hepa cells transfected with the Ala186-Ser187 mutant H2-histamine receptor (maximum response = 280 ± 15% above control). The response to low dose epinephrine (10−11 to 10−9 M) was inhibited with both cimetidine and propranolol while the response to high epinephrine concentrations (10−8 to 10−4 M) remained sensitive only to propranolol. Consistent with our previous studies, histamine stimulated cAMP generation in Hepa cells expressing both wild-type and mutant H2 histamine receptors (data not shown).