Geng G, Gaspo R, Trabelsi F, Yamaguchi N
Group de Recherche sur le Système Nerveux Autonome, Faculté de Pharmacie, Université de Montréal, Québec, Canada.
Am J Physiol. 1997 Oct;273(4):R1339-45. doi: 10.1152/ajpregu.1997.273.4.R1339.
The aim of the present study was to investigate whether the dihydropyridine-sensitive L-type Ca2+ channel is operative in adrenal catecholamine (CA) secretion induced by a novel neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), in anesthetized dogs. Plasma CA concentrations in adrenal venous and aortic blood were determined by a high-performance liquid chromatography method. All drugs tested were locally infused into the left adrenal gland via the left adrenolumbar artery. PACAP, with the isoform consisting of 27 (PACAP-27) and 38 (PACAP-38) amino acid residues, significantly increased CA output in a dose-dependent manner, with doses ranging from 5 to 500 ng and 7 to 700 ng, respectively. However, the amplitude of epinephrine response to PACAP-27 was three times greater than that obtained with PACAP-38 at the highest dose tested. In a separate group, a single dose of PACAP-27 (50 ng) induced highly reproducible CA responses when the same dose was repeated with an interval of 35 min. In dogs treated with nifedipine (50 microg), 5 min before the second administration of PACAP-27, the net CA response was significantly inhibited by approximately 50% compared with that obtained in the presence of vehicle. A similar CA response to BAY K 8644 (5 microg) was completely abolished by the same dose of nifedipine. The present results indicate that both PACAP-27 and PACAP-38 have the direct local secretagogue effect on the adrenal medulla in vivo and that CA responses to PACAP-27 were greater than those observed with PACAP-38 at equivalent mole doses. The study suggests that the dihydropyridine-sensitive L-type Ca2+ channel is functionally involved in PACAP-induced adrenal CA secretion in the canine adrenal medulla in vivo.
本研究的目的是探讨在麻醉犬中，对二氢吡啶敏感的L型Ca2+通道是否参与由一种新型神经肽——垂体腺苷酸环化酶激活多肽（PACAP）诱导的肾上腺儿茶酚胺（CA）分泌。采用高效液相色谱法测定肾上腺静脉血和主动脉血中的血浆CA浓度。所有受试药物均通过左肾上腺腰动脉局部注入左肾上腺。由27个（PACAP - 27）和38个（PACAP - 38）氨基酸残基组成的PACAP同工型，分别以5至500 ng和7至700 ng的剂量，以剂量依赖性方式显著增加CA分泌量。然而，在最高测试剂量下，肾上腺素对PACAP - 27的反应幅度比PACAP - 38大三倍。在另一组实验中，当以35分钟的间隔重复给予相同剂量（50 ng）的PACAP - 27时，能诱导出高度可重复的CA反应。在第二次给予PACAP - 27前5分钟，用硝苯地平（50微克）处理的犬，与给予溶媒时相比，净CA反应显著被抑制约50%。相同剂量的硝苯地平可完全消除对BAY K 8644（5微克）的类似CA反应。目前的结果表明，PACAP - 27和PACAP - 38在体内对肾上腺髓质均有直接的局部促分泌作用，并且在等效摩尔剂量下，CA对PACAP - 27的反应大于对PACAP - 38的反应。该研究提示，对二氢吡啶敏感的L型Ca2+通道在体内犬肾上腺髓质中功能性地参与了PACAP诱导的肾上腺CA分泌。
