Serone A P, Wright C E, Angus J A
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Br J Pharmacol. 1999 May;127(1):99-108. doi: 10.1038/sj.bjp.0702519.
Neuropeptide Y (NPY) has been proposed as the candidate inhibitory peptide mediating interactions between sympathetic and vagal neurotransmission in several species, including man. Here, we have defined the NPY receptors involved in modulation of cardiac autonomic neurotransmission using receptor-selective agonists and antagonists in the rabbit and guinea-pig isolated right atria. In isolated atrial preparations, sympathetically-mediated tachycardia (ST; with atropine 1 microM) or vagally-mediated bradycardia (VB; with propranolol 0.1-1 microM) in response to electrical field stimulation (EFS, 1-4 pulses) were tested 0-30 min after incubation with single concentrations of vehicle, NPY (0.01-10 microM), the Y2 receptor agonist N-Acetyl-[Leu28,31]NPY(24-36) (termed N-A[L]NPY(24-36)) or the Y1 receptor agonist [Leu31,Pro34]NPY (LP). The effect of NPY on the concentration-chronotropic response curves to isoprenaline and bethanechol were also assessed. Guinea-pig atria: NPY and N-A[L]NPY(24-36) caused concentration-dependent inhibition of VB and ST to EFS. Both peptides caused maximal inhibition of VB and ST within 10 min incubation and this remained constant. LP caused a concentration-dependent, transient inhibition of ST which was antagonized by the Y1-receptor antagonist GR231118 (0.3 microM), with apparent competitive kinetics. Rabbit atria: NPY (1 or 10 microM) had no effect on VB at any time point, but both NPY and LP caused a transient (approximately 10 min) inhibition of sympathetic tachycardia. This inhibition could be prevented by 0.3 microM GR231118. N-A[L]NPY(24-36) had no effect on ST. NPY had no effect on the response to beta-adrenoceptor stimulation by isoprenaline nor muscarinic-receptor stimulation by bethanechol in either species. Thus, in the guinea-pig, NPY causes a stable inhibition of both VB and ST to EFS via Y2 receptors and transient inhibition of ST via Y1 receptors. In contrast in the rabbit, NPY has no effect on the cardiac vagus and prejunctional inhibition of ST is transient and mediated by a Y1-like receptor (rather than Y2). Therefore it would be surprising if NPY plays a functional role in modulation of cardiac neurotransmission in the rabbit.
神经肽Y（NPY）已被认为是介导包括人类在内的多种物种交感神经与迷走神经神经传递相互作用的候选抑制性肽。在此，我们使用受体选择性激动剂和拮抗剂，在兔和豚鼠离体右心房中确定了参与调节心脏自主神经传递的NPY受体。在离体心房标本中，在与单一浓度的溶媒、NPY（0.01 - 10 μM）、Y2受体激动剂N - 乙酰 - [亮氨酸28,31]NPY(24 - 36)（称为N - A[L]NPY(24 - 36)）或Y1受体激动剂[亮氨酸31,脯氨酸34]NPY（LP）孵育0 - 30分钟后，测试电场刺激（EFS，1 - 4个脉冲）引起的交感神经介导的心动过速（ST；使用1 μM阿托品）或迷走神经介导的心动过缓（VB；使用0.1 - 1 μM普萘洛尔）。还评估了NPY对异丙肾上腺素和氨甲酰甲胆碱浓度 - 变时反应曲线的影响。豚鼠心房：NPY和N - A[L]NPY(24 - 36)对EFS引起的VB和ST产生浓度依赖性抑制。两种肽在孵育10分钟内对VB和ST产生最大抑制，且这种抑制保持恒定。LP对ST产生浓度依赖性、短暂性抑制，该抑制被Y1受体拮抗剂GR231118（0.3 μM）拮抗，表现出明显的竞争性动力学。兔心房：NPY（1或10 μM）在任何时间点对VB均无影响，但NPY和LP均对交感神经介导的心动过速产生短暂性（约10分钟）抑制。这种抑制可被0.3 μM GR231118阻止。N - A[L]NPY(24 - 36)对ST无影响。NPY对两种动物中异丙肾上腺素刺激β - 肾上腺素受体或氨甲酰甲胆碱刺激毒蕈碱受体的反应均无影响。因此，在豚鼠中，NPY通过Y2受体对EFS引起的VB和ST产生稳定抑制，并通过Y1受体对ST产生短暂性抑制。相比之下，在兔中，NPY对心脏迷走神经无影响，对ST的节前抑制是短暂的，由一种Y1样受体（而非Y2）介导。因此，如果NPY在兔心脏神经传递调节中发挥功能作用，那将是令人惊讶的。
