title: Different pathways of calcium sensitization activated by receptor agonists and phorbol esters in vascular smooth muscle.
abstract: 1. It has been shown that receptor agonists and activators of protein kinase C, phorbol esters, increase Ca2+ sensitivity of contractile elements in vascular smooth muscle. To discover if protein kinase C is involved in the agonist-mediated Ca2+ sensitization, we examined the effects of receptor agonists in the rat isolated aorta in which protein kinase C activity had been diminished by pretreatment with phorbol 12-myristate 13-acetate for 24 h. 2. In the aorta with protein kinase C activity, a high concentration (1 microM) of 12-deoxyphorbol 13-isobutyrate induced contraction and a low concentration (100 nM) potentiated high K(+)-induced contraction. In addition, prostaglandin F2 alpha induced greater contractions than high K+ at a given cytosolic Ca2+ level. The maximally effective concentrations of noradrenaline and endothelin-1 also induced greater contraction than high K+. In the aorta without protein kinase C activity, the contraction induced by 12-deoxyphorbol 13-isobutyrate and its potentiation of the high K(+)-induced contraction were abolished. However, prostaglandin F2 alpha, noradrenaline and endothelin-1 still induced a greater contraction than high K+. 3. In the aorta without protein kinase C activity, noradrenaline, endothelin-1 and prostaglandin F 2 alpha, but not 12-deoxyphorbol 13-isobutyrate, induced contractions in the presence of the Ca2+ channel blocker, verapamil, or in the absence of external Ca2+, by increasing Ca2+ sensitivity. 4. In the permeabilized preparations, inhibition of protein kinase C activity abolished the effect of potentiation of the Ca(2+)-induced contraction by 12-deoxyphorbol 13-isobutyrate although the potentiation of the contraction by prostaglandin F2 alpha did not change. 5. These results suggest that there are two pathways for Ca2+ sensitization in rat aorta; a protein kinase C-dependent pathway which is activated by phorbol esters, and a protein kinase C-independent pathway which is activated by receptor agonists.
authors.affiliation: Department of Veterinary Pharmacology, Faculty of Agriculture, University of Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hori
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.forename: S
authors.initials: S
authors.lastname: Miyamoto
authors.forename: H
authors.initials: H
authors.lastname: Ozaki
authors.forename: H
authors.initials: H
authors.lastname: Karaki
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015237:Dinoprost / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010539:Permeability; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D010703:Phorbol Esters; C039067:12-deoxyphorbol 13-isobutyrate; D004533:Egtazic Acid; D015237:Dinoprost; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium