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Involvement of protein kinase C activation in α2-adrenoceptor-mediated contractions of rabbit saphenous vein

https://doi.org/10.1016/0014-2999(95)00054-OGet rights and content

Abstract

The role of protein kinase C α2-adrenoceptor-induced contractions of rabbit saphenous vein was investigated. Contractions induced by the α2-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. α2-Adrenoceptor stimulation failed to increase [3H]myo-inositol 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 α2-adrenoceptors and that diacylglycerol derived from receptor-initiated phospholipase D activity may provide protein kinase C stimulation.

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