Effect of cholera enterotoxin on pacemaker rate and cyclic adenosine 3':5'-monophosphate in isolated rabbit...

The positive chronotropic effect of cholera enterotoxin on isolated rabbit sinoatrial (S-A) node was investigated. This toxin produced a time and dose-related increase in pacemaker rate and cyclic adenosine 3':5'-monophosphate (cyclic AMP) levels and shifted to the left the dose-response curves of norepinephrine on the pacemaker rate and cyclic AMP content in the S-A node. Thus, the sensitivity of the S-A node to norepinephrine was increased by the toxin. These effects of the toxin were not blocked by propranolol. There was a linear relation between the increases in pacemaker rate and cyclic AMP content after application of both the toxin and norepinephrine. However, the slope of the regression line relating pacemaker rate to cyclic AMP level differed with these two agents. These results suggest that cholera enterotoxin increases pacemaker rate with activation of the adenylate cyclase system in the S-A node, but the mechanism differs from that of norepinephrine.