Kulkarni Kaustubh H, Opere Catherine A, LeDay Angela M, Shara Mohd A, Ohia Sunny E
Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, 141 Science and Research Building 2, TX 77204, USA.
Neurochem Res. 2006 Jul;31(7):891-7. doi: 10.1007/s11064-006-9093-z. Epub 2006 Jun 29.
In the present study, we investigated the effect of histamine on sympathetic neurotransmission from isolated, superfused bovine irides. We also studied the pharmacology of prejunctional histamine receptors that regulate the release of norepinephrine (NE) from this tissue. The effect of exogenous histamine and various histamine receptor agonists was examined on the release of [(3)H]-norepinephrine ([(3)H]NE) triggered by electrical field stimulation using the Superfusion Method. Histamine receptor agonists caused a concentration-dependent inhibition of field-stimulated [(3)H]NE overflow with the following rank order of potency: imetit > histamine > R-alpha-methylhistamine. In all cases, the inhibitory action of histamine receptor agonists was attenuated at high concentrations of these compounds. The histamine receptor antagonists, clobenpropit (H(3)-antagonist/H(4)-agonist) and thioperamide (H(3)-antagonist) blocked the inhibitory response elicited by R-alpha-methylhistamine and imetit, respectively. Inhibitory effects of R-alpha-methylhistamine and clonidine were not additive suggesting that prejunctional H(3)- and alpha(2)-adrenoceptors coexist at neurotransmitter release sites. We conclude that histamine produces an inhibitory action on sympathetic neurotransmission in the bovine iris, an effect mimicked by selective H(3)-receptor agonists and blocked by H(3)-antagonists.
在本研究中，我们研究了组胺对分离的、经超灌流的牛虹膜交感神经传递的影响。我们还研究了调节该组织去甲肾上腺素（NE）释放的突触前组胺受体的药理学特性。使用超灌流法，检测了外源性组胺和各种组胺受体激动剂对电场刺激触发的[³H] - 去甲肾上腺素（[³H]NE）释放的影响。组胺受体激动剂对电场刺激引起的[³H]NE溢出产生浓度依赖性抑制，其效力顺序如下：碘甲噻丁＞组胺＞R - α - 甲基组胺。在所有情况下，这些化合物高浓度时组胺受体激动剂的抑制作用减弱。组胺受体拮抗剂氯苯丙哌嗪（H₃拮抗剂/H₄激动剂）和硫丙酰胺（H₃拮抗剂）分别阻断了R - α - 甲基组胺和碘甲噻丁引起的抑制反应。R - α - 甲基组胺和可乐定的抑制作用无相加性，提示突触前H₃和α₂肾上腺素能受体共存于神经递质释放部位。我们得出结论，组胺对牛虹膜的交感神经传递产生抑制作用，这种作用可被选择性H₃受体激动剂模拟，并被H₃拮抗剂阻断。
