Effects of drugs on the extracellular spaces of smooth muscle in vitro

Abstract

Summary The influx and efflux of the extracellular marker 14 C-inulin in the isolated gastric-fundal smooth muscle follow multiexponential kinetics. Inulin appeared to enter not only the extracellular spaces (ESP) but also less accessible compartments after a long incubation. Pre-incubation with a range of non-agonistic drugs affected both influx and efflux kinetics. The total inulin spaces (IS) during influx were increased by papaverine, TH (a papaverine-derivative), morphine and codeine, but they were decreased by atropine, dibenamine, promethazine, chlorpnomazine, LSD, psilocybin and methysergide. The analysis of the efflux curves showed that most of drugs induced a shift of inulin from the slow (intracellular?) to the fast (ESP) compartment, thus reflecting the increases of IS during influx. Promethazine and chlorpromazine decreased the swelling and acted mainly on the slow compartment and the non-exchangeable inulin (bound fraction), thus the decrease of IS appeared to be related to a loss of water from tissues and/or to the membrane-stabilizing action of both drugs. Psilocybin and, to a lesser extent, LSD and methysergide, increased the radioactivity exchanged in the fast compartment, but decreased the IS, probably due to less inulin-acoessible water available for diffusion rather than to a true effect on ESP.