Influence of some common methylxanthines on contractile responses and calcium mobilization of ileal, vas deferens and bladder smooth muscle.

Caffeine and theophylline (0.1-5.0 mM) relaxed rat ileal muscle and reduced spontaneous rhythmicity. They inhibited the K-induced tonic contractures of rat vas deferens and bladder muscle strips but were without significant effect on the phasic responses to K. Theobromine (1.0-2.5 mM) induced contractures in ileal muscle and enhanced both the phasic and tonic components of K-induced contractures in vas deferens and bladder muscle strips. Theophylline and caffeine inhibited by varying degrees the 45Ca efflux from ileal, vas deferens and bladder muscle strips during the slow intracellular phase, but theobromine significantly stimulated 45Ca slow compartment efflux in all three types of muscle. Caffeine and theophylline both depressed, to varying degrees, the 45Ca influx into all three muscles while theobromine stimulated 45Ca influx in all cases. Caffeine and theophylline were either without much effect or slightly stimulated calcium binding by microsomes and mitochondria isolated from ileum, vas deferens and bladder, while theobromine significantly inhibited calcium binding by both sub-cellular fractions in all three muscles. The inhibitory action of caffeine and theophylline on these muscles appears to be due to inhibition of calcium influx coupled with some stimulation of intracellular binding. Theobromine's excitatory action appears to be related to stimulation of calcium influx and inhibition of cellular calcium binding.