Distribution of N-type Ca2+ channel binding sites in rabbit brain following central administration of omega-conotoxin GVIA.
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.
Whorlow
S L
SL
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Loiacono
R E
RE
Angus
J A
JA
Wright
C E
CE
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D008978:Mollusk Venoms / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D011817:Rabbits; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D008978:Mollusk Venoms; D010455:Peptides; D020866:omega-Conotoxin GVIA