omega-Conotoxins block neurotransmission in the rat vas deferens by binding to different presynaptic sites on the N-type Ca2+ channel

omega-Conotoxins block neurotransmission in the rat vas deferens by binding to different presynaptic sites on the N-type Ca2+ channel

Author Hirata, H. Google Scholar
Albillos, A. Google Scholar
Fernandez, F. Google Scholar
Medrano, J. Google Scholar
Jurkiewicz, A. Google Scholar
Garcia, A. G. Google Scholar
Institution UNIV AUTONOMA MADRID
Universidade Federal de São Paulo (UNIFESP)
Abstract Electrically-induced twitch responses of the prostatic segment of vas deferens (0.1 Hz, 65 V, 1 ms) are mainly due to the transient presynaptic release of ATP, which acts postsynaptically on non-adrenergic receptors to contract smooth muscle cells. These responses were fully blocked by nanomolar concentrations of the omega-conotoxins GVIA, MVIIA, and MVIIC, most likely by inhibiting Ca2+ entry through presynaptic N-type Ca2+ channels controlling the release of ATP. Repeated washout of the toxins allowed the recovery of contractions, except for omega-conotoxin GVIA, whose inhibitory effects remained unchanged for at least 60 min. in addition, micromolar concentrations of omega-conotoxin MVIIC were unable to protect against the irreversible inhibition of twitch contractions induced by nanomolar concentrations of omega-conotoxin GVIA, At low extracellular Ca2+ concentrations (1.5 mM), 20 nM of omega-conotoxin GVIA or MVIIA inhibited completely the twitch contractions in about 10 min. in 5 mM Ca2+ the blockade of twitch contractions after 10 min was 70% for both toxins. in 1.5 mM Ca2+ omega-conotoxin MVIIC (1 mu M) inhibited completely the twitch contraction after 10 min. in 5 mM Ca2+ blockade developed very slowly and was very poor after 30 min, omega-conotoxin MVIIC depressed the response by only 20%. These results are compatible with the idea that the three omega-conotoxins block the purinergic neurotransmission of the vas deferens by acting on presynaptic N-type voltage-dependent Ca2+ channels. However, omega-conotoxin MVIIC seems to bind to sites different from those recognised by omega-conotoxin GVIA and MVIIA, which are markedly differentiated by their Ca2+ requirements for binding to their receptors.
Keywords Ca2+ channel
omega-conotoxin GVIA
omega-conotoxin MVIIA
omega-conotoxin MVIIC
omega-agatoxin IVA
vas deferens
purinergic neurotransmission
Language English
Date 1997-02-26
Published in European Journal of Pharmacology. Amsterdam: Elsevier B.V., v. 321, n. 2, p. 217-223, 1997.
ISSN 0014-2999 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 217-223
Origin http://dx.doi.org/10.1016/S0014-2999(96)00951-X
Access rights Closed access
Type Article
Web of Science ID WOS:A1997WL45700011
URI http://repositorio.unifesp.br/handle/11600/25694

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