Activation of PAC1 and VPAC receptor subtypes elicits differential physiological responses from sympathetic preganglionic neurons in the anaesthetized rat

作者：Inglott Melissa A; Lerner Ethan A; Pilowsky Paul M^*; Farnham Melissa M J

来源：British Journal of Pharmacology, 2012, 167(5): 1089-1098.

DOI：10.1111/j.1476-5381.2012.02045.x

• PACAP
• vasoactive intestinal polypeptide
• maxadilan
• PACAP(6-38)
• blood pressure
• sympathetic
• adrenaline
• noradrenaline
• adrenal medulla

BACKGROUND AND PURPOSE Pituitary adenylate cyclase-activating polypeptide (PACAP) is an excitatory neuropeptide with central and peripheral cardiovascular actions. Intrathecal PACAP increases splanchnic sympathetic nerve activity and heart rate, but not mean arterial pressure (MAP). We hypothesize that the three PACAP receptors (PAC1, VPAC1 and VPAC2) have different actions in central cardiovascular control, and that their summed effect results in the lack of MAP response observed following intrathecal PACAP injection. EXPERIMENTAL APPROACH The effects of the PACAP receptors on baseline cardiovascular parameters were investigated using selective agonists and antagonists administered into the intrathecal space of urethane-anaesthetized, vagotomized and artificially ventilated male Sprague-Dawley rats. KEY RESULTS Selective activation of the PACAP receptors had different effects on MAP. When activated by maxadilan, PAC1 receptors increased MAP. The VPAC receptors decreased MAP when both were activated with vasoactive intestinal polypeptide or when only VPAC1 receptors were activated. The PAC1 and VPAC2 receptor antagonist PACAP(638) had no cardiovascular effects, suggesting that PACAP is not tonically released. CONCLUSIONS AND IMPLICATIONS PACAP neurotransmission was not responsible for the moment-to-moment tonic regulation of central cardiovascular control mechanisms. Nevertheless, PACAP release within the spinal cord may have pleiotropic effects on sympathetic outflow depending on the postsynaptic receptor type. PAC1 and VPAC receptor subtypes produced opposing changes in blood pressure when activated by intrathecal PACAP-38 in the anaesthetized Sprague-Dawley rat, resulting in no net change in MAP.

• 出版日期2012-11