Effects of chronic reserpine administration on beta adrenergic receptors, adenylate cyclase and phosphodiesterase of the rat submandibular gland.

Chronic administration of reserpine to rats resulted in a doubling of the density of beta adrenergic receptors in submandibular gland membranes as determined by [3H]dihydroalprenolol binding. The affinity of the labelled drug for the receptor were not altered. There was a concomitant increase in the isoproterenol-stimulated cyclic AMP levels in slices of the gland when incubated in the absence of a phosphodiesterase inhibitor. However, this increase in cyclic AMP accumulation appears to be related to a decrease in phosphodiesterase activity rather than to the increase in the density of beta receptors, since glands from control and reserpinized animals accumulated equal amounts of cyclic AMP when incubated in the presence of a phosphodiesterase inhibitor. In addition, there was no difference between glands from controls and reserpine-treated rats in catecholamine-stimulated adenylate cyclase activity, but the Vmax of the phosphodiesterase was decreased 36% in glands from the treated animals. Similar results were obtained when control and surgically denervated glands were compared. The increase in beta adrenergic receptors appears to be the result of the depletion of norepinephrine due to reserpine administration, whereas the decreased phosphodiesterase activity may result from decreased cyclic AMP levels, secondary to the decrease in norepinephrine.