Netti C, Sibilia V, Guidobono F, Pecile A
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Italy.
Neuroendocrinology. 1993 Jun;57(6):1066-70. doi: 10.1159/000126472.
The effects of histamine (HA) and of (R) alpha-methyl-histamine (alpha-MeHA; a drug that decreases histaminergic tone through activation of presynaptic H3 receptors) on growth hormone (GH) secretion induced by clonidine (CLO), an alpha 2-adrenergic agonist, were examined in rats. HA (0.1 mumol/rat intracerebroventricularly) and alpha-MeHA (10 mg/kg i.a.) were administered 5 min and 3 h, respectively, before CLO (0.25 mg/kg i.a.). Blood samples for hormone determination were drawn from freely moving rats at various times before and after drug treatment. To characterize the mechanisms underlying the inhibition of GH secretion by HA, the effect of HA on GH induced by CLO was examined in rats depleted of catecholamine by pretreatment (2 h before) with alpha-methyl-p-tyrosine (alpha-MpT, 200 mg/kg s.c.) and in rats depleted of somatostatin by pretreatment (4 h before) with cysteamine (300 mg/kg s.c.). HA completely suppressed the GH-releasing effect of CLO whereas alpha-MeHA significantly enhanced the GH response to CLO. Neither alpha-MpT nor cysteamine pretreatment modified the inhibitory activity of HA on GH secretion elicited by CLO. The present results indicate that the inhibitory activity of brain HA on GH release consequent to activation of central alpha 2-receptors does not involve a modulatory action on catecholaminergic or somatostatinergic neurons but probably other mechanisms like the modulation of neurons synthetizing GH-releasing hormone.
在大鼠中研究了组胺（HA）和（R）α-甲基组胺（α-MeHA；一种通过激活突触前H3受体降低组胺能张力的药物）对α2-肾上腺素能激动剂可乐定（CLO）诱导的生长激素（GH）分泌的影响。HA（0.1 μmol/大鼠，脑室内注射）和α-MeHA（10 mg/kg，腹腔注射）分别在CLO（0.25 mg/kg，腹腔注射）前5分钟和3小时给药。在药物治疗前后的不同时间，从自由活动的大鼠采集血样用于激素测定。为了阐明HA抑制GH分泌的潜在机制，在通过预先（提前2小时）用α-甲基对酪氨酸（α-MpT，200 mg/kg，皮下注射）耗竭儿茶酚胺的大鼠以及通过预先（提前4小时）用半胱胺（300 mg/kg，皮下注射）耗竭生长抑素的大鼠中，研究了HA对CLO诱导的GH的影响。HA完全抑制了CLO的GH释放作用，而α-MeHA显著增强了GH对CLO的反应。α-MpT和半胱胺预处理均未改变HA对CLO引起的GH分泌的抑制活性。目前的结果表明，脑内HA对中枢α2受体激活后GH释放的抑制作用不涉及对儿茶酚胺能或生长抑素能神经元的调节作用，而可能涉及其他机制，如对合成生长激素释放激素的神经元的调节作用。
