Effect of cGMP Derivatives on Contraction Relaxation Cycle, Release of Norepinephrine and Protein Kinase Activity in Guinea Pig Vas Deferens

Abstract

Contractions of the guinea pigs vas deferens were induced by field stimulation and the effects of derivatives of cGMP were tested on the contraction-relaxation cycle. Relaxation was induced by 8-Br-cGMP and O2'-mb-cGMP. On the contrary, db-cGMP and N2-mb-cGMP potentiated the contraction. The relaxant effect of 8-Br-cGMP was not mimicked by 8-Br-5'GMP, instead the latter caused the opposite effect. Since neither 8-Br-cGMP nor db-cGMP affected the release of norepinephrine on field stimulation the cGMP derivatives induced their effects at a postsynaptic site. 8-Br-cGMP was found to be 100-fold more potent than cGMP to simulate protein kinase activity in crude extracts from guinea pig was deferens. N2-mb-cGMP and O2'-mb-cGMP were approximately equipotent to cGMP while db-cGMP was less active. 8-Br-5'-GMP did not stimulate the protein kinase. It is suggested that the results support the hypothesis that cGMP acts as a relaxant in the smooth muscle of the vas deferens. The potentiation caused by db-cGMP and N2-mb-cGMP on contractions could be dependent on the substitution in the guanine moiety of the molecules with the butyryl group. Their effect was thus probably unrelated to a specific cGMP effect.