Regulation of autonomic receptors in rat submandibular gland

Abstract

The binding of receptor specific radioligands to autonomic receptors in the rat submandibular gland was characterized after chronic drug administration and surgical sympathetic denervation. Reserpine administration resulted in an up-regulation of both alpha 2-adrenergic receptors labeled by [3H]clonidine and beta 1-adrenergic receptors labeled by [3H]dihydroalprenolol. The increase in alpha 2-receptors was half-maximal 24 hr after a single injection of reserpine, and was about 10-fold greater than control after seven daily injections. By contrast, the beta-adrenergic receptor density was the same as control after 3 days of reserpine administration, but within 7 days was about 2-fold greater than control. Guanethidine or yohimbine administration also resulted in an up-regulation of alpha 2-adrenergic receptors. Reserpine administration or unilateral superior cervical ganglionectomy increased the density of alpha 1-adrenergic receptor binding sites 24-80%. Norepinephrine and methoxamine, but not clonidine, caused potassium to be released from submandibular gland slices. Prazosin, but not yohimbine, blocked this response to norepinephrine, indicating that the response was mediated by alpha 1-adrenergic receptors. Potassium release elicited by alpha 1-agonists was augmented in slices from animals that received reserpine. Neither drug treatment nor sympathetic denervation altered muscarinic cholinergic receptor binding. The densities of muscarinic and beta-adrenergic receptors were found to be 23-51% higher in glands from female rats than in glands from male rats.