Integrated autonomic and behavioral responses to L/N Ca2(+)-channel blocker omega-conotoxin in conscious rats.

Article date: 1990/9/1

PubMed ID: 1697739

Journal name: The American journal of physiology (ISSN: 0002-9513)


omega-Conotoxin (omega-ctx) was used as a probe for studying the putative role of brain L/N-type Ca2+ channels in regulation of autonomic functions. Rats were injected intracerebroventricularly (icv) with omega-ctx, and hemodynamic, biochemical and behavioral variables were monitored. omega-Ctx (0.032-10 nmol/kg) caused a persistent, dose-dependent shaking behavior, complex thermoregulatory changes, and motor deficits lasting up to 48 h. Cardiovascular responses to omega-ctx included tachycardia (+71 +/- 16%, P less than 0.01) and elevated arterial blood pressure (+16 +/- 1%, P less than 0.05) associated with increased circulating levels of norepinephrine and epinephrine. Higher doses, 1 or 10 nmol/kg, resulted in circulatory shock and death. Central administration of 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester (TMB-8), diltiazem (100 or 1,000 nmol/kg), neomycin (100 nmol/kg, each), nifedipine (10 nmol/kg), and CdCl2 (100 nmol/kg), which represent intracellular, non-specific N-, L-, and L/N-type Ca2(+)-channel blockers, respectively, did not cause any behavioral or hemodynamic effects, whereas the L-channel agonist BAY K 8644 (100 nmol/kg icv) caused a mild transient pressor response. Pretreatment with the gamma-aminobutyric acid (GABA) agonist muscimol (icv) or a combined intravenous pretreatment with propranolol and N-methylatropine blocked the omega-ctx effects. Our data suggest that omega-ctx actions in the brain involve central GABAergic mechanisms modulated by yet a different type of Ca2+ channels not characterized by any of the known voltage-operated Ca2+ channels.

Author List: Shapira S, Adeyemo O M, Feuerstein G

Publication Types: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.

Substances mentioned in the article: Calcium Channel Blockers; Catecholamines; Peptides, Cyclic; omega-Conotoxins; Conus magus toxin; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Diltiazem;

Mesh terms: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester/pharmacology; Animals; Autonomic Nervous System/drug effects; Behavior, Animal/drug effects; Blood Chemical Analysis; Body Temperature/drug effects; Calcium Channel Blockers/pharmacology; Catecholamines/blood; Diltiazem/pharmacology; Hemodynamics/drug effects; Injections, Intraventricular; Male; Motor Activity/drug effects; Nervous System/drug effects; Peptides, Cyclic/pharmacology; Rats; Rats, Inbred Strains; omega-Conotoxins;

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