PROTEIN-KINASE C-MEDIATED CONTRACTILE RESPONSE OF THE RAT VAS-DEFERENS

The role of protein kinase C (PKC) in mediating contractile responses in the rat vas deferens was studied. Phorbol-12,13-diacetate (PDA) in the presence of 20 mM K+ elicited a concentration-dependent response with an EC50 of 190 nM. The non-PKC activator 4-alpha-phorbol (2-mu-M) was unable to elicit contraction in 20 mM K+ buffer. Incubation of rat vas deferens with the PKC inhibitor iso-H7 (30-mu-M) attenuated the response to norepinephrine (NE) and neurokinin A, with maximal effects depressed to 42 and 39% of control, respectively. Responses to 60 mM K+ and 2-mu-M PDA (20 mM K+) was also significantly inhibited by iso-H7. In the presence of 2-mu-M PDA and 20 mM K+, the NE concentration-effect curve was shifted 3.6-fold to the right of the control curve in a parallel manner. 4-alpha-Phorbol (20 mM K+) at the same concentration did not produce this effect. These results suggest a significant role for PKC in the contractile response of the rat vas deferens.