Secretin-induced changes in rate,contractility and adenylate cyclase activity in rat heart atria

1. Secretin stimulated adenylate cyclase activity in crude membrane preparations from right and left rat atria, when tested in the presence of the potentiating activator forskolin. Its maximal effect on adenylate cyclase activity was greater in the right atrium than in the left atrium but the peptide efficiency was lower, in both atria, than that ofD, l-isoproterenol.
2. Secretin stimulated the rate of contraction of the spontaneously beating right atrium, but less efficiently thanD,l-isoproterenol. Although this positive chronotropic action of secretin was inhibited byD,l-propranolol, it was probably not mediated by the release of endogenous catecholamines as: a) the inhibitory effects ofD-andL-propranolol were similar and b) the efficiency of secretin on the in vitro beating of right atrium was the same in control and reserpinized rats.
3. Secretin stimulated the force of contraction of spontaneously beating right atria, even in the presence of propranolol, i.e. when the chronotropic effect of secretin was abolished. The hormone exerted also a positive inotropic effect on the electrically stimulated rat atrium. This effect was blocked neither by tetrodotoxin nor by propranolol.
4. When comparing the dose-effect curves of secretin andD,l-isoproterenol on adenylate cyclase activation on the one hand, and on the stimulation of rate and contractility on the other hand, it is tempting to suggest that cyclic AMP might be involved in the modulation by secretin of the mechanical properties of rat atria.