title: 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.
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism
chemical_list: D011494:Protein Kinases; D006152:Cyclic GMP; D009638:Norepinephrine