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.
Institute of Pharmacology and Therapeutics, Faculty of Medicine, Porto, Portugal.
J P
JP
Nunes
A
A
Mota
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D000068438:Brimonidine Tartrate; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D017275:Isradipine / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D010656:Phenylephrine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D012501:Saphenous Vein / Q000187:drug effects / Q000201:enzymology
D000316:Adrenergic alpha-Agonists; D000477:Alkylating Agents; D007546:Isoquinolines; D010879:Piperazines; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D015240:Phorbol 12,13-Dibutyrate; C051731:chlorethylclonidine; D000068438:Brimonidine Tartrate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D003000:Clonidine; D017275:Isradipine