Li B, Chik C L, Ho A K, Karpinski E
Departments of Physiology and Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2H7.
Endocrinology. 2001 Jul;142(7):2865-73. doi: 10.1210/endo.142.7.8229.
Pituitary adenylate cyclase-activating polypeptide (PACAP), a vasoactive peptide, modulates the L-type Ca(2+) channel current (L channel current) in vascular smooth muscle cells (VSMC) through activation and integration of two intracellular pathways, protein kinase A and protein kinase C (PKC). In the present study we compared the effects of PACAP on the L channel current in VSMC from the spontaneously hypertensive rats (SHR) and normotensive controls, Wistar Kyoto rats (WKY). We found that compared with WKY, VSMC from SHR had a higher L channel current density. Stimulation by PACAP (10 nM) caused an increase in the amplitude of the whole cell current and prolonged open time in VSMC from SHR and WKY, with the increase greater in SHR. These effects of PACAP on the L channel current was mimicked by an activator of PKC. In contrast, PACAP caused a smaller increase in cAMP accumulation in VSMC from SHR than WKY, and there was no difference in the inhibitory effect of 8-bromo-cAMP on the L channel current from both type of cells. The greater increase in amplitude of the L channel current by PACAP in VSMC from SHR persisted in the presence of adenosine cyclic 3',5'-monophosphothioate, Rp-isomer, a cAMP antagonist, but not calphostin C, a PKC inhibitor. Taken together, our results show an increase in L channel current density and an enhanced PACAP effect on the L channel current in VSMC from SHR compared with WKY. This difference in PACAP response appears to be predominately secondary to an increased PKC sensitivity.
垂体腺苷酸环化酶激活多肽（PACAP）是一种血管活性肽，它通过激活和整合蛋白激酶A和蛋白激酶C（PKC）这两条细胞内信号通路，调节血管平滑肌细胞（VSMC）中的L型钙通道电流（L通道电流）。在本研究中，我们比较了PACAP对自发性高血压大鼠（SHR）和正常血压对照Wistar Kyoto大鼠（WKY）血管平滑肌细胞L通道电流的影响。我们发现，与WKY相比，SHR的血管平滑肌细胞具有更高的L通道电流密度。用PACAP（10 nM）刺激后，SHR和WKY的血管平滑肌细胞全细胞电流幅度增加，开放时间延长，其中SHR增加更为明显。PKC激活剂可模拟PACAP对L通道电流的这些作用。相反，PACAP引起SHR血管平滑肌细胞中cAMP积累的增加幅度小于WKY，并且8-溴-cAMP对两种细胞L通道电流的抑制作用没有差异。在存在cAMP拮抗剂腺苷环3',5'-单磷酸硫代酯Rp-异构体的情况下，PACAP使SHR血管平滑肌细胞L通道电流幅度的更大增加仍然存在，但PKC抑制剂钙磷蛋白C不存在这种情况。综上所述，我们的结果表明，与WKY相比，SHR血管平滑肌细胞的L通道电流密度增加，且PACAP对L通道电流的作用增强。PACAP反应的这种差异似乎主要是由于PKC敏感性增加所致。
