caa a22 4500 467935084 CHVBK 20180406152954.0 cr unu---uuuuu 170328e20060401xx s 000 0 eng 10.1007/s00408-005-2567-y doi (NATIONALLICENCE)springer-10.1007/s00408-005-2567-y Effect of PKC Isozyme Inhibition on Forskolin-Induced Activation of BKCa Channels in Rat Pulmonary Arterial Smooth Muscle [Elektronische Daten] [Shu Zhu, Richard White, Scott Barman] Signaling mechanisms that elevate cyclic AMP (cAMP) activate large-conductance, calcium- and voltage-activated potassium (BKCa) channels in vascular smooth muscle and cause vasodilatation. In pulmonary vascular smooth muscle (PVSM), BKCa channel modulation is important in the regulation of pulmonary arterial pressure, and inhibition (closing) of the BKCa channel causes pulmonary vasoconstriction. Protein kinase C (PKC) modulates BKCa channels in systemic vascular smooth muscle, but little is known about the effect of PKC on BKCa channel activity in PVSM. A novel finding from our laboratory showed that PKC activates BKCa channels in rat pulmonary arterial smooth muscle and, having observed that cAMP-elevating agents also open BKCa channels, we hypothesized that PKC may open BKCa channels via a cAMP-dependent mechanism. Forskolin (10μM), an activator of adenylyl cyclase, which increases cAMP concentration, opened BKCa channels in single pulmonary arterial smooth muscle cells (PASMC) of the Sprague-Dawley rat. The effect of forskolin was completely blocked by the PKC inhibitor Go 6983, which selectively blocks the α, β, δ, γ, and ζ PKC isozymes, and, by rottlerin, which selectively inhibits PKCδ, and partially blocked by Go 6976, which selectively inhibits PKCα PKCβ, and PKCμ. These results indicate that specific PKC isozymes mediate forskolin-induced activation of BKCa channels in PASMC, which suggests that a signaling pathway involving PKC activation and cAMP exists in pulmonary arterial smooth muscle to open BKCa channels. Springer Science+Business Media, Inc., 2006 Protein kinase C nationallicence Forskolin nationallicence Pulmonary nationallicence BKCa channels nationallicence cAMP nationallicence Zhu Shu Department of Pharmacology and Toxicology, Medical College of Georgia, 1170 15th street, 30912, Augusta, Georgia, USA aut White Richard Department of Pharmacology and Toxicology, Medical College of Georgia, 1170 15th street, 30912, Augusta, Georgia, USA aut Barman Scott Department of Pharmacology and Toxicology, Medical College of Georgia, 1170 15th street, 30912, Augusta, Georgia, USA aut Lung Springer-Verlag; www.springer-ny.com 184/2(2006-04-01), 89-97 0341-2040 184:2<89 2006 184 408 https://doi.org/10.1007/s00408-005-2567-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00408-005-2567-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhu Shu Department of Pharmacology and Toxicology, Medical College of Georgia, 1170 15th street, 30912, Augusta, Georgia, USA aut NATIONALLICENCE 700 1- White Richard Department of Pharmacology and Toxicology, Medical College of Georgia, 1170 15th street, 30912, Augusta, Georgia, USA aut NATIONALLICENCE 700 1- Barman Scott Department of Pharmacology and Toxicology, Medical College of Georgia, 1170 15th street, 30912, Augusta, Georgia, USA aut NATIONALLICENCE 773 0- Lung Springer-Verlag; www.springer-ny.com 184/2(2006-04-01), 89-97 0341-2040 184:2<89 2006 184 408 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer