The effects of chronic administration of chloroquine and quinacrine on the response of normal and denervated smooth muscle to agonist drugs

Abstract

The functional effects of chronic administration of 60 mg kg −1 chloroquine or quinacrine given as daily intraperitoneal injections for 84 days on normal and denervated expansor secundariorum muscles, a smooth muscle from the wing of chicks wholly innervated by noradrenergic nerves, have been investigated. Administration of quinacrine, but not chloroquine, blocked responses to noradrenergic nerve stimulation. Surgical denervation abolished responses to nerve stimulation. Contraction of the expansor muscle induced by noradrenaline was not changed by chronic administration of chloroquine or quinacrine, and both drugs did not influence denervation supersensitivity of expansor muscles to noradrenaline. Expansor muscles were unresponsive to acetylcholine (ACh) and histamine, but muscles from chicks chronically treated with chloroquine and quinacrine were responsive to ACh and histamine. Denervation also restored the response of expansor muscles to ACh and histamine and the responses were greater for denervated muscles from chronically treated chicks; these changes were more marked with quinacrine. Expansor muscles were contracted by potassium chloride (KCl) and 5-hydroxytryptamine (5-HT), and chronic treatment increased the responsiveness of expansor muscles to KCl. Denervation increased the responsiveness of expansor muscles to KCl and 5-HT; this effect was more pronounced in denervated muscles from quinacrine-treated chicks. The findings indicate that chronic administration of quinacrine sensitizes smooth muscles to agonist drugs by blocking noradrenergic transmission to induce postjunctional changes and exerting a direct action on the smooth muscle; these actions are less pronounced with chloroquine administration.