Malinowska B, Godlewski G, Schlicker E
Department of Pharmacodynamics, Medical University, Bialystok, Poland.
J Physiol Pharmacol. 1998 Jun;49(2):191-211.
The histamine H3 receptor was initially identified as a presynaptic autoreceptor controlling histamine release and synthesis in the brain. It belongs to the superfamily of G protein-coupled receptors. The existence of the H3 receptor which has not yet been cloned was definitely established by the design of highly potent and selective agonists (R-(-)-alpha-methylhistamine, imetit) and antagonists (thioperamide, clobenpropit). These receptors also occur as heteroreceptors both in the central nervous system and on peripheral neurons of the gastrointestinal and bronchial tract, where they regulate the release of a variety of neurotransmitters. In the cardiovascular system, histamine H3 receptors are mainly located presynaptically on the postganglionic sympathetic nerve fibers innervating the blood vessels and the heart. Their activation leads to the inhibition of noradrenaline release and consequently to the reduction of the neurogenic vasopressor and cardiostimulatory responses. The presence of such receptors has been shown both in vitro (human, pig, guinea-pig, rabbit, rat isolated tissues) and in vivo (rat, guinea-pig). The vascular and cardiac presynaptic H3 receptors may be activated by endogenous histamine. The vascular H3 receptors appear to be operative in hypertension and interact with presynaptic alpha 2-adrenoceptors. Postsynaptic vasodilatatory H3 receptors have been detected in several vascular beds as well. H3 receptor ligands affect basal cardiovascular parameters in conscious and anesthetized guinea-pigs but not rats. Presynaptic H3 receptors may play a role in the pathophysiology of headache and cardiac ischemia.
组胺H3受体最初被鉴定为一种控制大脑中组胺释放和合成的突触前自身受体。它属于G蛋白偶联受体超家族。通过设计高效且选择性的激动剂（R-(-)-α-甲基组胺、碘替丁）和拮抗剂（硫代哌酰胺、氯苯丙哌嗪），明确证实了尚未克隆的H3受体的存在。这些受体也作为异受体存在于中枢神经系统以及胃肠道和支气管的外周神经元上，在那里它们调节多种神经递质的释放。在心血管系统中，组胺H3受体主要位于突触前，存在于支配血管和心脏的节后交感神经纤维上。它们的激活导致去甲肾上腺素释放受到抑制，并因此导致神经源性血管升压和心脏刺激反应减弱。这种受体的存在已在体外（人、猪、豚鼠、兔、大鼠离体组织）和体内（大鼠、豚鼠）得到证实。血管和心脏的突触前H3受体可能被内源性组胺激活。血管H3受体似乎在高血压中起作用，并与突触前α2-肾上腺素能受体相互作用。在几个血管床中也检测到了突触后血管舒张性H3受体。H3受体配体影响清醒和麻醉豚鼠的基础心血管参数，但不影响大鼠。突触前H3受体可能在头痛和心脏缺血的病理生理学中起作用。
