Effects of noradrenergic denervation on alpha-1 adrenoceptors and receptor-stimulated contraction of chick expansor secundariorum muscle

K Williams, T Bennett and PG Strange

Alpha-1 adrenoceptors were identified in the chick expansor secundariorum (ESM) smooth muscle by ligand binding (using [3H]prazosin) and organ bath techniques. We examined the effects of both reversible (6-hydroxydopamine-induced) and irreversible (surgical) noradrenergic denervation on alpha-1 adrenoceptors in the ESM. We also measured, in vitro, muscle contraction stimulated by the alpha-1 adrenoceptor agonist methoxamine and by 5-hydroxytryptamine. After both surgical and chemical denervation there were decreases in the number of [3H] prazosin binding sites in the ESM. After reversible denervation the decrease in receptor number persisted during a period in which there was extensive reinnervation of the muscle. At a time (7 days after injection) when the ESM was partially reinnervated the maximum methoxamine-stimulated response, but not that of 5-hydroxytryptamine, was reduced. After surgical (but not chemical) denervation there were increases in both protein content and wet weight of the muscle. However, at 7 days after denervation, these effects alone could not account for the observed decrease in receptor number. A small increase in sensitivity (1.4-fold) to methoxamine and a much larger increase in sensitivity (4.5-fold) to 5-hydroxytryptamine developed after surgical denervation but there appeared to be nonspecific decreases in maximum responses to the agonists. It is concluded that both surgical and chemical denervation produced a decrease in alpha-1 adrenoceptor number in the ESM; this may have contributed to the decrease in maximum contractile response. After surgical denervation a nonspecific supersensitivity developed in the ESM; it may be that a nonspecific contribution to methoxamine-stimulated responses was less apparent due to the loss of alpha-1 adrenoceptors.

Volume 241, Issue 3, pp. 939-949, 06/01/1987
Copyright © 1987 by American Society for Pharmacology and Experimental Therapeutics