Effects of chemical denervation on β1- and β2-adreno-ceptors

Abstract

Effects of chemical denervation by reserpine or 6-hydroxy-dopamine(6-OHDA) on β-adrenoceptor-adenylate cyclase system in rats were studied.The changes of 3H-dihydroalprenolol binding sites(Bmax) estimated by Scatchard analysis and c-AMP contents (basal(B) and isoproterenol stimulated(S) c-AMP) induced by the chemical denervations were monitored.Both reserpine(0.25mg/kg s.c. for 3days) and 6-OHDA(50mg/kg i.v. for 2days) reduced norepinephrine content(NE) in cardiac and lung tissues more than 90% (chemical denervation). The reserpine treatment produced a significant reduction of cardiac Bmax and basal c-AMP,while S to B ratio(S/B) was increased (supersensitivity).In lung tissue, however,reserpine did not influence Bmax, basal c-AMP and S/B significantly. The treatment of 6-OHDA also produced a significant decrease of Bmax and basal c-AMP in cardiac and lung tissues,but S/B was unchanged in both tissues.After a wash out period of 6-OHDA for 5days,NE and Bmax in lung returned to control value,while in cardiac tissue,they did not return completely.These findings suggest that the alteration of Bmax and basal c-AMP associated with the chemical denervations did not correlate with S/B.In reserpine treated lymphocytes, a significant increase in basal c-AMP and decrease of S/B were observed, while Bmax remained the control value.The reduction of S/B by reserpine was also observed in vitro.