TY - JOUR T1 - EARLY PRE- AND POSTJUNCTIONAL EFFECTS OF 6-HYDROXYDOPAMINE JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 49 LP - 62 VL - 178 IS - 1 AU - G. HAEUSLER Y1 - 1971/07/01 UR - http://jpet.aspetjournals.org/content/178/1/49.abstract N2 - 6-Hydroxydopamine (6-OHDA) was injected i.v. into cats and rats in doses sufficient to produce chemical sympathectomy. The functional changes occurring 30 minutes to 14 hours after its administration at the pre- and postjunctional site of the adrenergic neuroeffector junction were studied in pithed rats and in isolated organ preparations (nictitating membrane and heart of the cat, mesenteric arteries of the rat). 6-OHDA caused a long-lasting indirect sympathomimetic effect. Since this effect was calcium-dependent, it is suggested that one of the earliest changes produced by 6-OHDA in the membrane of the adrenergic nerve endings is an increase in calcium permeability. Sixty minutes after injection of 6-OHDA, the response to sympathetic nerve stimulation was abolished in the isolated organs. Asynchronous antidromic discharges, evoked by acetylcholine or KCl in terminal parts of cardiac adrenergic fibers, were reduced in amplitude 30 minutes after 6-OHDA and had virtually disappeared after 60 minutes. The absence of both the response to sympathetic nerve stimulation and antidromic discharges indicated that, at an early stage of the 6-OHDA-induced degeneration, the membrane of the adrenergic nerve endings had lost its ability to conduct and/or to generate action potentials. However, the amine pump in the membrane of adrenergic nerve terminals of isolated nictitating membranes seemed to be intact for up to three hours after 6-OHDA. Fourteen hours after the administration of 6-OHDA, denervation supersensitivity was fully developed in the isolated nictitating membrane. At the postjunctional site, evidence for a noncompetitive long-lasting alpha adrenergic blockade was obtained in isolated mesenteric arteries of the rat after a high dose of 6-OHDA. © 1971, by The Williams & Wilkins Company ER -