Significant role of neuronal non-N-type calcium channels in the sympathetic neurogenic contraction of rat mesenteric artery.
1. The possible involvement of pre-junctional non-N-type Ca2+ channels in noradrenaline (NA)-mediated neurogenic contraction by electrical field stimulation (EFS) was examined pharmacomechanically in the isolated rat mesenteric artery. 2. EFS-generated contraction of endothelium-denuded mesenteric artery was frequency-dependent (2 - 32 Hz) and was abolished by tetrodotoxin (TTX, 1 microM), guanethidine (5 microM) or prazosin (100 nM), indicating that NA released from sympathetic nerve endings mediates the contractile response. 3. NA-mediated neurogenic contractions to lower frequency stimulations (2 - 8 Hz) were almost abolished by an N-type Ca2+ channel blocker, omega-conotoxin-GVIA (1 microM) whereas the responses to higher frequency stimulations (12 - 32 Hz) were less sensitive to omega-conotoxin-GVIA. The omega-conotoxin-GVIA-resistant component of the contractile response to 32 Hz stimulation was inhibited partly (10 - 20%) by omega-agatoxin-IVA (10 - 100 nM; concentrations which are relatively selective for P-type channels) and to a greater extent by omega-agatoxin-IVA (1 microM) and omega-conotoxin-MVIIC (3 microM), both of which block Q-type channels at the concentrations used. 4. omega-Agatoxin-IVA (10 - 100 nM) alone inhibited 32 Hz EFS-induced contraction by 10 approximately 20% whereas omega-conotoxin-MVIIC (3 microM) alone inhibited the response by approximately 60%. 5. These omega-toxin treatments did not affect the contractions evoked by exogenously applied NA. 6. These findings show that P- and Q-type as well as N-type Ca2+ channels are involved in the sympathetic neurogenic vascular contraction, and suggest the significant role of non-N-type Ca2+ channels in NA release from adrenergic nerve endings when higher frequency stimulations are applied to the nerve.
Tanaka
Y
Y
Department of Pharmacology, Toho University School of Pharmaceutical Sciences, 2-2-1 Miyama, Funabashi-City, Chiba 274-8510, Japan.
Mochizuki
Y
Y
Tanaka
H
H
Shigenobu
K
K
D000818:Animals; D020864:Calcium Channels, N-Type / Q000145:classification / Q000502:physiology*; D020865:Calcium Channels, P-Type / Q000145:classification / Q000502:physiology; D020907:Calcium Channels, Q-Type / Q000145:classification / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013379:Substrate Specificity; D013564:Sympathetic Nervous System / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D020867:omega-Agatoxin IVA / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology; D020960:omega-Conotoxins / Q000494:pharmacology
D020864:Calcium Channels, N-Type; D020865:Calcium Channels, P-Type; D020907:Calcium Channels, Q-Type; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; C075851:omega-conotoxin-MVIIC; D013779:Tetrodotoxin; D020866:omega-Conotoxin GVIA; D009638:Norepinephrine