Ca²⁺ dependent but PKC independent signalling mediates UTP induced contraction of rat mesenteric arteries

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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 Ca²⁺ 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 Ca²⁺. UTP attenuation of both voltage-gated (K_v) and ATP-dependent (K_ATP) K⁺ currents was abolished when intracellular Ca²⁺ was decreased from 100 to 20 nM. PKC inhibition reduced slightly the ability of UTP to attenuate K_v currents but had no effect on K_ATP current inhibition. In conclusion, both UTP induced contraction of mesenteric artery and the inhibition of K_v and K_ATP currents of mesenteric artery smooth muscle cells by UTP are relatively independent of PKC activation; furthermore, the inhibition of both K_v and K_ATP currents requires intracellular Ca²⁺.