Epibatidine, an alkaloid from the poison frog Epipedobates tricolor, is a powerful ganglionic depolarizing agent.
Epibatidine, an alkaloid from the poison frog Epipedobates tricolor, is a powerful ganglionic depolarizing agent.
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发表时间：
1994-08
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通讯作者：
M. Fisher;D. Huangfu;T. Shen;P. Guyenet
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作者：
M. Fisher;D. Huangfu;T. Shen;P. Guyenet
Epibatidine是一种新发现的来自Dendrobatidae青蛙皮肤的生物碱，与尼古丁具有结构相似性。我们研究了地棘蛙素对心肺功能和神经节突触传递的影响。在麻醉、麻痹和人工通气的大鼠上级颈或内脏交感神经放电（sSND）和膈神经放电（PND）随动脉压（AP）的变化进行记录。低剂量（0.5-2 μ g/kg）地棘蛙素静脉给药导致AP和sSND一过性增加，随后降低并恢复至基线;该低剂量地棘蛙素还导致PND呈剂量依赖性增加。在高剂量下（累积剂量为8-16微克/kg），地棘蛙素导致心动过缓、sSND的深度抑制和PND的短暂消除。静脉注射神经节阻滞剂氯异松达明（5 mg/kg）后，AP仍增加1 μ g/kg地棘蛙素（+39 +/-11 mm Hg）。用α-1肾上腺素能拮抗剂酚妥拉明（+40 +/-10 mmHg）预处理不改变这种升压作用;然而，用加压素拮抗剂[β-巯基-β，β-环戊亚甲基丙酰基1，O-ET-Tyr 2，Val 4，Arg 8]加压素（50微克/千克静脉注射; +2 +/- 0.4 mm Hg）。低剂量的地棘蛙素（0.5-2微克/千克）在分散的神经节制备物中产生节后神经元的放电，并增强突触传递;在高剂量（累积剂量为8-16微克/千克）下，生物碱阻断神经节突触传递。这些结果表明，地棘蛙素是一种有效的神经节烟碱受体激动剂和生物碱elimentarily心肺功能的尼古丁类似。
Epibatidine, a newly discovered alkaloid from the skin of Dendrobatidae frogs, has structural similarities to nicotine. We examined the effects of epibatidine on cardiorespiratory function and ganglionic synaptic transmission. Superior cervical or splanchnic sympathetic nerve discharge (sSND) and phrenic nerve discharge (PND) were recorded along with arterial pressure (AP) in urethane-anesthetized, paralyzed and artificially ventilated rats. Epibatidine administered i.v. at low doses (0.5-2 micrograms/kg) produced a transient increase in AP and sSND, followed by a decrease and return to baseline; this low dose of epibatidine also produced a dose-dependent increase in PND. At high doses (cumulative dose of 8-16 micrograms/kg), epibatidine produced bradycardia, a profound depression in sSND and a transient elimination of PND. After i.v. administration of the ganglionic blocker chlorisondamine (5 mg/kg), AP was still increased by 1 microgram/kg epibatidine (+39 +/- 11 mm Hg). This pressor effect was not altered by pretreatment with the alpha-1 adrenergic antagonist phentolamine (+40 +/- 10 mm Hg); however, it was blocked by additional pretreatment with the vasopressin antagonist [beta-mercapto-beta,beta-cyclopentamethylenepropiony1, O-ET-Tyr2,Val4,Arg8]vasopressin (50 micrograms/kg i.v.; +2 +/- 0.4 mm Hg). Low doses of epibatidine (0.5-2 micrograms/kg) produced firing of postganglionic neurons in a decentralized ganglion preparation and potentiated synaptic transmission; at high doses (cumulative dose of 8-16 micrograms/kg), the alkaloid blocked ganglionic synaptic transmission. These results suggest that epibatidine is a potent agonist of ganglionic nicotinic receptors and that the alkaloid elicits cardiorespiratory effects similar to those of nicotine.