title: Excitatory effect of histamine on rat spinal motoneurons by activation of both H₁ and H₂ receptors in vitro.
abstract: The central histaminergic nervous system, originating from the tuberomammillary nucleus of the hypothalamus, widely innervates almost the whole brain as well as the spinal cord. However, the effect of histamine on spinal motoneurons, the final common path for motor control, is still unknown. By using 8-14-day-old rat spinal slice preparations and intracellular recordings, the effect of histamine on motoneurons in lumbar spinal cord and the underlying mechanisms were studied. Bath application of histamine (30-300 μM) induced a membrane depolarization in the majority of recorded spinal motoneurons (78/90, 86%). Perfusing slices with tetrodotoxin or low-Ca(2+) /high-Mg(2+) medium did not block the histamine-induced excitation, indicating a direct postsynaptic action of histamine on motoneurons. Separate application of the selective histamine H(1) receptor antagonist mepyramine or the selective histamine H(2) receptor antagonist ranitidine partially suppressed the histamine-induced excitation, whereas a combination of ranitidine and mepyramine totally blocked the excitatory effect of histamine on motoneurons. On the other hand, both the selective histamine H(1) receptor agonist 2-pyridylethylamine and the selective histamine H(2) receptor agonist dimaprit mimicked the excitation of histamine on spinal motoneurons. These agonist-induced excitations were also blocked by mepyramine or ranitidine. Furthermore, histamine affected membrane input resistance and potentiated repetitive firing behavior of spinal motoneurons. These results demonstrate that histamine excites rat spinal motoneurons via the histamine H(1) and H(2) receptors and increases their excitability, suggesting that the hypothalamospinal histaminergic fibers may directly modulate final motor outputs and actively regulate ongoing motor execution andspinal motor reflexes.
authors.affiliation: Department of Biological Science and Technology and State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Guan-Yi
authors.initials: GY
authors.lastname: Wu
authors.forename: Xiao-Hu
authors.initials: XH
authors.lastname: Han
authors.forename: Qian-Xing
authors.initials: QX
authors.lastname: Zhuang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Wing-Ho
authors.initials: WH
authors.lastname: Yung
authors.forename: Ying-Shing
authors.initials: YS
authors.lastname: Chan
authors.forename: Jing-Ning
authors.initials: JN
authors.lastname: Zhu
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Wang
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D002121:Calcium Channel Blockers / Q000494:pharmacology; D017259:Dimaprit / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006632:Histamine / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D009046:Motor Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D011725:Pyridines / Q000494:pharmacology; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D011970:Receptors, Histamine H2 / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D017442:Histamine Agonists; D006635:Histamine H2 Antagonists; D011725:Pyridines; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D013779:Tetrodotoxin; D006632:Histamine; D011899:Ranitidine; C006183:2-(2-aminoethyl)pyridine; D017259:Dimaprit