PROTEIN-KINASE-C AND ALPHA-2-ADRENOCEPTOR-MEDIATED INHIBITION OF NORADRENALINE RELEASE FROM THE RAT TAIL ARTERY

In isolated rat tail arteries preincubated with [H-3]noradrenaline, electrical field stimulation evoked the overflow of tritium. Phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activating phorbol ester, time-dependently increased the overflow at 1-mu-mol/L but not at 0.1-mu-mol/L. In contrast, the overflow was not altered by phorbol 13-acetate (PA, 1-mu-mol/L), which does not influence the activity of PKC. Polymyxin B (70-mu-mol/L), an inhibitor of PKC, depressed the overflow when given alone and, in addition, attenuated the effect of PMA, 1-mu-mol/L. The selective alpha-2-adrenoceptor agonist B-HT 933 depressed the overflow; PMA, 1-mu-mol/L, did not interfere with the effect of B-HT 933, 10-mu-mol/L. The results provide evidence for the participation of prejunctionally located PKC in the release of noradrenaline. However, PKC does not seem to be involved in the alpha-2-adrenoceptor-agonist-mediated inhibition of noradrenaline release.