title: Ca2+ dependent but PKC independent signalling mediates UTP induced contraction of rat mesenteric arteries.
abstract: Uridine triphosphate (UTP) can be released from damaged cells to cause vasoconstriction. Although UTP is known to act through P2Y receptors and PLC activation in vascular smooth muscle, the role of PKC in generating the response is somewhat unclear. Here we have used Tat-linked membrane permeable peptide inhibitors of PKC to assess the general role of PKC and also of specific isoforms of PKC in the UTP induced contraction of rat mesenteric artery. We examined the effect of PKC inhibition on UTP induced contraction, increased cytoplasmic Ca(2+) and reduction of K(+) currents and found that PKC inhibition caused a relatively small attenuation of contraction but had little effect on changes in cytoplasmic Ca(2+). UTP attenuation of both voltage-gated (Kv) and ATP-dependent (KATP) K(+) currents was abolished when intracellular Ca(2+) was decreased from 100 to 20 nM. PKC inhibition reduced slightly the ability of UTP to attenuate Kv currents but had no effect on KATP current inhibition. In conclusion, both UTP induced contraction of mesenteric artery and the inhibition of Kv and KATP currents of mesenteric artery smooth muscle cells by UTP are relatively independent of PKC activation; furthermore, the inhibition of both Kv and KATP currents requires intracellular Ca(2+).
authors.affiliation: Departments of Cell Physiology & Pharmacology, University of Leicester, Leicester, UK.
authors.forename: Fouzia
authors.initials: F
authors.lastname: Panhwar
authors.forename: Richard D
authors.initials: RD
authors.lastname: Rainbow
authors.forename: Robert
authors.initials: R
authors.lastname: Jackson
authors.forename: Noel W
authors.initials: NW
authors.lastname: Davies
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D066298:In Vitro Techniques; D054086:KATP Channels / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D014544:Uridine Triphosphate / Q000494:pharmacology*
chemical_list: D054086:KATP Channels; D024642:Potassium Channels, Voltage-Gated; D011493:Protein Kinase C; D002118:Calcium; D014544:Uridine Triphosphate