Contrasting effects of phorbol esters on serotonin- and vasopressin-evoked contractions in rat aorta and small mesenteric artery.
Phorbol esters, which activate protein kinase C, modulate vasoconstrictor-induced tension in vascular smooth muscle. We examined the effects of phorbol esters (phorbol 12,13-dibutyrate [PDBu] and 12-O-tetradecanoylphorbol 13-acetate [TPA]) on receptor agonist (serotonin [5-HT] and arginine vasopressin [AVP])-, high K(+)-, and caffeine-induced contractions in rings of rat aorta and a small (second-order) branch of the superior mesenteric artery (SMA). PDBu and TPA significantly augmented agonist-evoked contractions in aorta but diminished those in SMA. For example, 30 nM PDBu increased 5-HT- and AVP-evoked contractions 2.0-2.5-fold in aorta (p less than 0.01) but decreased 5-HT- and AVP-induced contractions by 40-60% in SMA (p less than 0.01). In contrast, PDBu and TPA amplified high K(+)- and 10 mM caffeine-induced contractions in both aorta and SMA. Augmentation of agonist-induced contractions by PDBu was greater in endothelium-denuded aorta than in intact aorta. Two protein kinase C antagonists, H-7 and staurosporine, inhibited 5-HT-evoked contractions in the absence as well as in the presence of PDBu in both types of arteries. The augmentation of contractile responses to caffeine and K+ by phorbol esters in both types of arteries suggests that the phorbols increase the sensitivity of the contractile apparatus to Ca2+, probably by activating protein kinase C. However, the inhibitory effects of phorbols on 5-HT- and AVP-evoked responses in SMA suggest that under these conditions the dominant effect of the phorbols is a marked reduction in the availability of Ca2+ in the SMA but not in the aorta.
Shima
H
H
Department of Physiology, University of Maryland School of Medicine, Baltimore 21201.
Blaustein
M P
MP
D000818:Animals; D001013:Aorta, Thoracic; D001127:Arginine Vasopressin / Q000494:pharmacology*; D066298:In Vitro Techniques; D008638:Mesenteric Arteries; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology*
D010703:Phorbol Esters; D001127:Arginine Vasopressin; D012701:Serotonin; D011493:Protein Kinase C