Molecular Pharmacology, Vol 19, 21-26, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

Effect of Long-Term Changes in Sympathetic Nervous Activity on the Beta-Adrenergic Receptor-Adenylate Cyclase Complex of Rat Pineal Gland

¹ Department of Pharmacology, Medical College of Pennsylvania, Philadelphia, Pennsylvania 19129

The effect of sympathetic input on beta-adrenergic receptors and adenylate cyclase activity of rat pineal gland was determined by surgically, chemically, or physiologically reducing the sympathetic input to the gland. Bilaterally decentralizing the superior cervical ganglia of blinded rats increased the density of beta-adrenergic receptors as measured by the binding of [³H]dihydroalprenolol, but did not change the affinity of the receptors for the ligand. The increased density of receptors following ganglionic decentralization was accompanied by an increase in norepinephrine-sensitive adenylate cyclase activity. An increase in the density of pineal gland beta-adrenergic receptors was also observed in rats that were chemically sympathectomized by administration of guanethidine or reserpine. In pineal glands isolated from rats treated with guanethidine as neonates, the accumulation of cyclic AMP in response to norepinephrine was greater than that found in glands from rats treated with 0.9% NaCl solution. Similarly, in pineal glands of rats treated with repeated doses of reserpine, there was an increase in norepinephrinesensitive adenylate cyclase activity as compared with that found in the glands from 0.9% NaCl-treated control animals. Maintaining rats in constant light, which physiologically reduces the sympathetic input to the pineal gland, also caused an increased density of beta-receptors in this gland. These experiments support the hypothesis that the increased responsiveness of catecholamine-sensitive adenylate cyclase seen in adrenergically innervated tissue following reduced sympathetic input is due to an increased density of beta-adrenergic receptors.

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ACKNOWLEDGMENT We acknowledge with thanks the excellent technical assistance of Ms. Becky Simon.