Evidence that chloroethylclonidine can contract the dog saphenous vein via a protein kinase C-dependent mechanism.

Chloroethylclonidine has recently been shown to produce concentration-dependent contractions in the dog saphenous vein. These contractions are very sensitive to cooling, yohimbine and rauwolscine, and moderately sensitive to prazosin. The effects of compound H-7 (a protein kinase inhibitor) and isradipine (a calcium channel blocker) on the contractions to chloroethylclonidine, UK14304 and phenylephrine were studied in the dog saphenous vein. Compound H-7 (20 mumol/l) produced a very marked (85%) inhibition of chloroethylclonidine-induced contractions, a moderate (48%) inhibition of UK14304-induced contractions and a slight (19%) inhibition of phenylephrine-induced contractions. Isradipine (1 mumol/l) produced a moderate (49%) inhibition of chlorethylclonidine-induced clonidine-induced contractions and a slight (15%) inhibition of phenylephrine-induced contractions. Phorbol 12,13-dibutyrate (1 mumol/l) produced a contraction that reached 61.1 +/- 3.2% of the maximum and was inhibited moderately (46%) by compound H-7. It is suggested that, in the dog saphenous vein, the receptor activated by chloroethylclonidine may be coupled to protein kinase C.