Bugajski A J, Thor P, Głód R, Gadek-Michalska A, Bugajski J
Department of Pathophysiology, Jagiellonian University School of Medicine, Cracow, Poland.
J Physiol Pharmacol. 2003 Dec;54(4):643-52.
Brain histamine participates in central regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Endogenous prostaglandins modulate signal transduction of different neurotransmitters involved in activation of HPA axis. In the present experiment we investigated whether endogenous prostaglandins are involved in the stimulation of ACTH and corticosterone secretion by histaminergic systems in the rat brain. Histamine (50 microg), histamine-trifluoromethyl-toluidine derivative (HTMT, 75microg) a selective and potent H(1)-receptor agonist, and amthamine (50 microg) a H(2)-receptor agonist given intracerebroventricularly (i.c.v.) to non-anesthetized rats considerably increased ACTH and corticosterone secretion 1h after administration. A non-selective cyclooxygenase inhibitor indomethacin (2 mg/kg i.p. or 10 microg i.c.v.), piroxicam (0.02 and 0.2 microg i.c.v.) a more potent antagonist of constitutive cyclooxygenase (COX-1) and compound NS-398 (0.1 and 1.0 microg i.c.v.), a selective inhibitor of inducible cyclooxygenase (COX-2) were given 15 min before histamine and histamine receptor agonists. One hour after the last injection trunk blood from decapitated rats was collected for hormones determination. The histamine-induced ACTH and corticosterone secretion was significantly diminished by piroxicam and was not markedly altered by indomethacin and compound NS-398. The HTMT-elicited increase in ACTH and corticosterone secretion was significantly prevented by indomethacin and was not affected by piroxicam or compound NS-398. The amthamine-evoked increase in ACTH and corticosterone secretion was not markedly influenced by any cyclooxygenase blocker applied in the present experiment. These results indicate that the histamine H(1)-receptor transmitted central stimulation of the HPA axis is considerably mediated by prostaglandins generated by consititutive cyclooxygenase, whereas stimulation transmitted via H(2)-receptor does not significantly depend on endogenous prostaglandins mediation.
脑内组胺参与下丘脑 - 垂体 - 肾上腺（HPA）轴的中枢调节。内源性前列腺素调节参与HPA轴激活的不同神经递质的信号转导。在本实验中，我们研究了内源性前列腺素是否参与大鼠脑内组胺能系统对促肾上腺皮质激素（ACTH）和皮质酮分泌的刺激作用。将组胺（50微克）、组胺 - 三氟甲基 - 甲苯胺衍生物（HTMT，75微克，一种选择性且强效的H(1)受体激动剂）和氨甲胺（50微克，一种H(2)受体激动剂）脑室内注射（i.c.v.）给未麻醉的大鼠，给药1小时后ACTH和皮质酮分泌显著增加。在给予组胺和组胺受体激动剂前15分钟，注射非选择性环氧化酶抑制剂吲哚美辛（2毫克/千克腹腔注射或10微克脑室内注射）、吡罗昔康（0.02和0.2微克脑室内注射，一种更强效的组成型环氧化酶（COX - 1）拮抗剂）和化合物NS - 398（0.1和1.0微克脑室内注射，一种诱导型环氧化酶（COX - 2）选择性抑制剂）。在最后一次注射1小时后，断头大鼠的躯干血被采集用于激素测定。吡罗昔康显著减少了组胺诱导的ACTH和皮质酮分泌，而吲哚美辛和化合物NS - 398未使其明显改变。吲哚美辛显著阻止了HTMT引起的ACTH和皮质酮分泌增加，而吡罗昔康或化合物NS - 398对此无影响。在本实验中应用的任何环氧化酶阻滞剂对氨甲胺引起的ACTH和皮质酮分泌增加均无明显影响。这些结果表明，组胺H(1)受体介导的HPA轴中枢刺激很大程度上由组成型环氧化酶产生的前列腺素介导，而通过H(2)受体介导的刺激并不显著依赖内源性前列腺素的介导。
