Involvement of protein kinase C activation in alpha 2-adrenoceptor-mediated contractions of rabbit saphenous vein.
The role of protein kinase C alpha 2-adrenoceptor-induced contractions of rabbit saphenous vein was investigated. Contractions induced by the alpha 2-adrenoceptor-selective agonist 5-bromo-6-[2-imidazolin-2-ylamino]-quinoline (UK14304) were inhibited by prior treatment with pertussis toxin and by Ca2+ removal, confirming a Gi/Go-dependent coupling pathway which was highly dependent upon Ca2+ influx. Protein kinase C inhibitors calphostin-C and staurosporine each caused a non-competitive inhibition of UK14304 response. Down-regulation of protein kinase C by pretreatment with tetradecanoylphorbol acetate reduced UK14304 response by almost 90% with no effect on contractions induced by elevated KCl. The ineffectiveness of L-type Ca2+ channel blockers and the absence of stimulated 45Ca2+ uptake or efflux by UK14304 indicated that phospholipid-derived products were most likely responsible for protein kinase C activation. alpha 2-Adrenoceptor stimulation failed to increase [3H]myoinositol phosphate formation, but caused a significant increase in the formation of both [32P]phosphatidic acid and diacylglycerol, indicating the possible activation of phospholipase D activity. These results suggest that protein kinase C is important for the vasoconstriction induced by alpha 2-adrenoceptors and that diacylglycerol derived from receptor-initiated phospholipase D activity may provide protein kinase C stimulation.
Aburto
T
T
Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
Jinsi
A
A
Zhu
Q
Q
Deth
R C
RC
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D000068438:Brimonidine Tartrate; D002118:Calcium / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004789:Enzyme Activation / Q000502:physiology; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009281:Naphthalenes / Q000494:pharmacology; D010712:Phosphatidic Acids / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D011817:Rabbits; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology*; D012501:Saphenous Vein / Q000187:drug effects / Q000378:metabolism; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000470:Alkaloids; D004075:Diglycerides; D007295:Inositol Phosphates; D009281:Naphthalenes; D010712:Phosphatidic Acids; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D000068438:Brimonidine Tartrate; D011493:Protein Kinase C; D010739:Phospholipase D; D019311:Staurosporine; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium