Whorlow S L, Loiacono R E, Angus J A, Wright C E
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Eur J Pharmacol. 1996 Nov 7;315(1):11-8. doi: 10.1016/s0014-2999(96)00592-4.
Central administration of the N-type Ca2+ channel blocker omega-conotoxin GVIA in conscious rabbits has previously been shown to result in a slowly developing hypotensive and sympatholytic effect, with peak changes observed after 48 h. The aim of the current study was to examine the distribution of [125I] omega-conotoxin GVIA binding in rabbit brain alone or following a prior i.c.v. injection of omega-conotoxin GVIA to determine the site(s) of action of centrally administered omega-conotoxin GVIA. Brains were removed from rabbits 2 or 48 h after central administration of vehicle or non-labelled omega-conotoxin GVIA (30 pmol/kg, i.c.v.). Brain sections were then incubated with [125I] omega-conotoxin GVIA (50 pM) and the density of specific [125I] omega-conotoxin GVIA binding measured in dpm/mm2 was determined by quantitative receptor autoradiography. In the vehicle group, highest densities of [125I] omega-conotoxin GVIA binding sites (> 20 dpm/mm2) were detected in cortex, caudate, putamen, and the stratum oriens and stratum radiatum of the hippocampus. Prior (48 h) i.c.v. injection of omega-conotoxin GVIA resulted in a decrease in specific binding of [125I] omega-conotoxin GVIA, particularly in cortex and some portions of the caudate and hippocampus. Lesser effects were observed with a prior (2 h) i.c.v. injection of omega-conotoxin GVIA. Central administration of omega-conotoxin GVIA may be acting to disrupt neurotransmission in higher brain regions which may, in turn, affect cardiovascular control mechanisms in the rabbit.
先前的研究表明，向清醒的兔子中枢给予N型钙通道阻滞剂ω-芋螺毒素GVIA会导致缓慢出现的降压和抗交感神经作用，48小时后观察到峰值变化。本研究的目的是单独检测兔脑中[125I]ω-芋螺毒素GVIA结合的分布情况，或在预先脑室内注射ω-芋螺毒素GVIA后进行检测，以确定中枢给予ω-芋螺毒素GVIA的作用位点。在向兔子中枢给予赋形剂或未标记的ω-芋螺毒素GVIA（30 pmol/kg，脑室内注射）后2或48小时，取出兔子的大脑。然后将脑切片与[125I]ω-芋螺毒素GVIA（50 pM）一起孵育，并通过定量受体放射自显影法测定以dpm/mm2为单位的特异性[125I]ω-芋螺毒素GVIA结合密度。在赋形剂组中，在皮质、尾状核、壳核以及海马的原层和辐射层中检测到[125I]ω-芋螺毒素GVIA结合位点的最高密度（>20 dpm/mm2）。预先（48小时）脑室内注射ω-芋螺毒素GVIA导致[125I]ω-芋螺毒素GVIA的特异性结合减少，尤其是在皮质以及尾状核和海马的某些部分。预先（2小时）脑室内注射ω-芋螺毒素GVIA观察到的影响较小。中枢给予ω-芋螺毒素GVIA可能是通过破坏大脑高级区域的神经传递来发挥作用，进而可能影响兔子的心血管控制机制。
