Formation, accumulation and release of adenosine 3′,5′-monophosphate induced by histamine in the superior cervical ganglion of the rat in vitro

Abstract

1. 1. Histamine increased endogeneous cyclic AMP levels and the conversion rate of 14 C-labeled adenine nucleotides to cyclic[ 14C]AMP in rat superior ganglia in vitro in a dose-related manner, with half-maximal stimulation at a concentration of about 2·10 −4 M. 2. 2. The accumulation of cyclic AMP could be blocked by antihistamine drugs. The H 2-blocker burimanide showed a strong stimulatory effect on adenylate cyclase in contrast to diphenhydramine. Practolol, a β-adrenergic antagonist, inhibited the accumulation of cyclic AMP induced by epinephrine, but not induced by histamine. 3. 3. Following stimulation of cyclic AMP formation in the ganglia, cyclic AMP concentrations also increased in the incubation medium, indicating overflow or release of the cyclic nucleotide from the ganglia. Marked release of cyclic[ 14C]-adenine occured under control or stimulation conditions. 4. 4. Measurable amounts of cyclic AMP phosphodiesterase and lactate dehydrogenase activity were detected in the medium in the course of incubation of ganglia. Cyclic AMP phosphodiesterase activity slightly decreased initially on stimulation of adenylate cyclase by histamine. No efflux of ATP or [ 24C]ATP was observed, except immediately after the transfer of ganglia from ice-cold to experimental (37°C) medium. 5. 5. p-(Di- n-popylsulfanoyl)-benzoic acid (10 −4 M) blocked the efflux of cyclic AMP by about 10%. It inhibited the accumulation by cyclic AMP induced by histamine, but not by epinephrine.