Selectivity of omega-conotoxin GVIA for n-type calcium channels in rat isolated small mesenteric arteries.
1. The selectivity of omega-conotoxin GVIA (omega-CTX) for prejunctional N-type voltage-operated calcium channels (VOCC) was examined in rat isolated small mesenteric arteries mounted in a Mulvany-Halpern myograph. Contractile responses to perivascular nerve stimulation, noradrenaline (NA) and potassium (K+) were obtained before and after treatment with omega-CTX. The effects of omega-CTX were compared with those of felodipine, an L-type VOCC blocker. 2. Omega-CTX (3 nmol/L-10 mu mol/L) inhibited contractions to electrical field stimulation by up to 94%, compared with the corresponding time control group. Felodipine (0.1 mu mol/L) had little effect on the contractions to electrical stimulation compared with the vehicle-treated vessels. 3. Concentration-response curves to exogenous NA (0.1 mu mol/L) and contractions to a submaximal concentration of K+ (50 mmol/L) were unaffected by omega-CTX (3 nmol/L-10 mu mol/L). In contrast, the maximum contraction to NA in vessels exposed to felodipine (0.1 mu mol/L) was reduced by 37%, and the contraction to K+ (62 mmol/L) was reduced by 84% compared with vehicle-treated arteries. 4. The results indicate that even at concentrations up to 10 mu mol/L (10 000-fold higher than required to inhibit prejunctional N-type VOCC), omega-CTX inhibits only neurotransmitter release. Its effects are clearly different to felodipine as omega-CTX has no effect on post-junctional alpha1-adrenoceptor-mediated vasoconstriction or direct smooth muscle depolarization considered to be mediated by L-type VOCC. Therefore, at least at the vascular neuroeffector junction, omega-CTX appears to be highly selective for N-type VOCC with no effect on L-type VOCC.
Whorlow
S L
SL
Department of Pharmacology, University of Melbourne, Victoria, Australia.
Angus
J A
JA
Wright
C E
CE
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015736:Felodipine / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D013997:Time Factors; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010455:Peptides; D020866:omega-Conotoxin GVIA; D015736:Felodipine; D009638:Norepinephrine