Release of creatine phosphokinase from muscle—I: Effect of polymyxin B, compound [formula omitted], and serotonin

Abstract

Polymyxin B and compound 48 80 produce marked increases in the plasma levels of type III (skeletal muscle) creatine phosphokinase (CPK) in the Sprague-Dawley rat. Two other mast cell disrupters, dextran and ovomucoid, which also produce anaphylactoid shock, as well as the mast cell disrupters d-tubocurarine, diphenhydramine and tripellenamine, do not affect plasma CPK (PCPK) levels. The mast cell constituents histamine and heparin do not increase PCPK levels, although significant increases were noted following high doses of exogenous serotonin (5-HT). The effect of 5-HT on PCPK levels was inhibited by methysergide but that of polymyxin B was not. The neuromuscular blockade produced by polymyxin B was considered to have little if any role in the increase in PCPK levels, since neither succinylcholine or d-tubocurarine increases PCPK levels. Preventing the hypothermia secondary to polymyxin B or 5-HT did not block the increase in PCPK levels following treatment with these agents. Incubation of isolated extensor digitorum longus muscle in vitro in the presence of polymyxin B and compound 48 80 increases the rate of efflux of CPK from the muscle. It is postulated that polymyxin B and compound 48 80 have a toxic effect on muscle, one manifestation of which could be increased efflux of CPK from muscle.