De Wildt D J, Van der Ven J C, Van Bergen P, De Lang H, Versteeg D H
Department of Medical Pharmacology, Rudolf Magnus Institute, Medical Faculty, Utrecht University, The Netherlands.
Naunyn Schmiedebergs Arch Pharmacol. 1994 Jan;349(1):50-6. doi: 10.1007/BF00178205.
In conscious and urethane-anesthetized rats intravenously (i.v.) administered gamma 2-melanocyte-stimulating hormone (gamma 2-MSH), a melanotropin derived from the precursor peptide pro-opiomelanocortin (POMC), has been shown to induce a pressor response combined with a tachycardia. A site of action within the hindbrain, e.g. the nucleus tractus solitarii (NTS) or the area postrema (AP), has been suggested. In order to test the postulate that gamma 2-MSH acts within these hindbrain regions, the peptide was microinjected into various parts of the NTS and into the AP of urethane-anesthetized rats and blood pressure (BP) and heart rate (HR) were measured. Injection of gamma 2-MSH (100-500 pmol) into the NTS resulted in a dose-dependent decrease in BP and HR rather than in the expected pressor and tachycardiac response which is generally found in conscious and urethane-anesthetized rats following i.v. administration of the peptide. With respect to the depressor and bradycardiac effect the melanotropin was far more potent when injected into the pars commissuralis than into the medial part of the NTS. The responses were maximal after 3-4 min and lasted for about 15 min. gamma 2-MSH had no effect when injected into the AP. It is noteworthy that also a hypotensive and bradycardic effect for gamma 2-MSH is found in pentobarbital-anesthetized rats following i.v. administration. Therefore, we conclude that in addition to a pressor and tachycardic response gamma 2-MSH can elicit an opposite effect by interaction with structures within a discrete region in the NTS, the pars commissuralis.(ABSTRACT TRUNCATED AT 250 WORDS)
在清醒和经氨基甲酸乙酯麻醉的大鼠中,静脉注射γ2-促黑素细胞激素(γ2-MSH),一种源自前体肽阿片促黑激素皮质素原(POMC)的促黑素,已被证明可诱导升压反应并伴有心动过速。有人提出其作用部位在后脑,例如孤束核(NTS)或最后区(AP)。为了验证γ2-MSH在后脑这些区域起作用的假设,将该肽微量注射到经氨基甲酸乙酯麻醉的大鼠的NTS各部位和AP中,并测量血压(BP)和心率(HR)。向NTS注射γ2-MSH(100 - 500 pmol)导致BP和HR呈剂量依赖性下降,而非清醒和经氨基甲酸乙酯麻醉的大鼠静脉注射该肽后通常出现的预期升压和心动过速反应。就降压和心动过缓作用而言,促黑素注射到连合部时比注射到NTS内侧部时作用更强。反应在3 - 4分钟后达到最大值,并持续约15分钟。γ2-MSH注射到AP中无作用。值得注意的是,在戊巴比妥麻醉的大鼠静脉注射后,γ2-MSH也有降压和心动过缓作用。因此,我们得出结论,除了升压和心动过速反应外,γ2-MSH可通过与NTS连合部离散区域内的结构相互作用引发相反的效应。(摘要截短至250字)