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. 1990 Oct;101(2):437–447. doi: 10.1111/j.1476-5381.1990.tb12727.x

Effects of omega-conotoxin GVIA on autonomic neuroeffector transmission in various tissues.

A De Luca 1, C G Li 1, M J Rand 1, J J Reid 1, P Thaina 1, H K Wong-Dusting 1
PMCID: PMC1917697  PMID: 2175236

Abstract

1. The effects of omega-conotoxin GVIA (conotoxin), a potent inhibitor of neuronal N-type Ca2+ channels, have been examined on responses to stimulation of noradrenergic, cholinergic and non-adrenergic, non-cholinergic (NANC) nerves in a range of isolated tissues to investigate the role of conotoxin-sensitive Ca2+ channels in neurotransmission. 2. Contractions elicited by field stimulation of noradrenergic nerves in rat and mouse anococcygeus muscles, rabbit ear artery and rat vas deferens (epididymal portion) were inhibited by conotoxin. Responses to noradrenaline, and to adenosine triphosphate in the vas deferens, were not affected. 3. Positive chronotropic responses to field stimulation of noradrenergic nerves were inhibited by conotoxin in rat and mouse atria, but responses to noradrenaline and tyramine were not affected. 4. The stimulation-induced release of noradrenaline was inhibited by conotoxin in the rabbit ear artery and in rat and mouse atria. 5. Relaxations in response to stimulation of the noradrenergic perivascular mesenteric nerves were reduced or abolished by conotoxin in rat and rabbit jejunum. The response to noradrenaline in rat jejunum was not affected. 6. Contractions elicited by stimulation of cholinergic nerves were inhibited by conotoxin in rat jejunum and mouse ileum (perivascular mesenteric nerves), and in guinea-pig taenia caeci (field stimulation). Responses to acetylcholine in rat jejunum and mouse ileum were not affected. 7. Contractions elicited by stimulation of the cholinergic plus NANC pelvic nerves were inhibited by conotoxin in rabbit colon, and to a lesser extent in guinea-pig colon. The stimulation-induced contraction of the guinea-pig colon was inhibited by conotoxin by a greater proportion in the presence than in the absence of atropine. Responses to acetylcholine were not affected in the rabbit colon but were slightly reduced in the guinea-pig colon. 8. Relaxations in response to field stimulation of NANC nerves were inhibited by conotoxin in guinea-pig taenia caeci and rat gastric fundus strips, and in rat anococcygeus muscle when the tone was raised by guanethidine but not when it was raised by carbachol. The relaxations produced by sodium nitroprusside in the rat gastric fundus and anococcygeus were not affected. 9. Contractions of the rat bladder elicited by stimulation of the peri-urethral nerves, which are NANC- and cholinergically mediated, were relatively insensitive to inhibition by conotoxin. The response were almost completely abolished by tetrodotoxin. 10. The conotoxin-induced inhibitions of responses to nerve stimulation developed slowly and persisted after removal of conotoxin.(ABSTRACT TRUNCATED AT 400 WORDS)

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Selected References

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  1. Augustine G. J., Charlton M. P., Smith S. J. Calcium action in synaptic transmitter release. Annu Rev Neurosci. 1987;10:633–693. doi: 10.1146/annurev.ne.10.030187.003221. [DOI] [PubMed] [Google Scholar]
  2. BURN J. H., RAND M. J. The relation of circulating noradrenaline to the effect of sympathetic stimulation. J Physiol. 1960 Feb;150:295–305. doi: 10.1113/jphysiol.1960.sp006388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Belai A., Ralevic V., Burnstock G. VIP release from enteric nerves is independent of extracellular calcium. Regul Pept. 1987 Oct;19(1-2):79–89. doi: 10.1016/0167-0115(87)90077-2. [DOI] [PubMed] [Google Scholar]
  4. Brock J. A., Cunnane T. C., Evans R. J., Ziogas J. Inhibition of transmitter release from sympathetic nerve endings by omega-conotoxin. Clin Exp Pharmacol Physiol. 1989 Apr;16(4):333–339. doi: 10.1111/j.1440-1681.1989.tb01568.x. [DOI] [PubMed] [Google Scholar]
  5. Brown D. A., Docherty J. R., French A. M., MacDonald A., McGrath J. C., Scott N. C. Separation of adrenergic and non-adrenergic contractions to field stimulation in the rat vas deferens. Br J Pharmacol. 1983 Jun;79(2):379–393. doi: 10.1111/j.1476-5381.1983.tb11010.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Burnstock G., Campbell G., Rand M. J. The inhibitory innervation of the taenia of the guinea-pig caecum. J Physiol. 1966 Feb;182(3):504–526. doi: 10.1113/jphysiol.1966.sp007834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Clasbrummel B., Osswald H., Illes P. Inhibition of noradrenaline release by omega-conotoxin GVIA in the rat tail artery. Br J Pharmacol. 1989 Jan;96(1):101–110. doi: 10.1111/j.1476-5381.1989.tb11789.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cruz L. J., Johnson D. S., Olivera B. M. Characterization of the omega-conotoxin target. Evidence for tissue-specific heterogeneity in calcium channel types. Biochemistry. 1987 Feb 10;26(3):820–824. doi: 10.1021/bi00377a024. [DOI] [PubMed] [Google Scholar]
  9. GARRY R. C., GILLESPIE J. S. An in vitro preparation of the distal colon of the rabbit with orthosympathetic and parasympathetic innervation. J Physiol. 1954 Mar 29;123(3):60P–61P. [PMC free article] [PubMed] [Google Scholar]
  10. GARRY R. C., GILLESPIE J. S. The responses of the musculature of the colon of the rabbit to stimulation, in vitro, of the parasympathetic and of the sympathetic outflows. J Physiol. 1955 Jun 28;128(3):557–576. doi: 10.1113/jphysiol.1955.sp005325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gibson A., Wedmore C. V. Responses of the isolated anococcygeus muscle of the mouse to drugs and to field stimulation. J Auton Pharmacol. 1981 Jun;1(3):225–233. doi: 10.1111/j.1474-8673.1981.tb00451.x. [DOI] [PubMed] [Google Scholar]
  12. Gillespie J. S. The rat anococcygeus muscle and its response to nerve stimulation and to some drugs. Br J Pharmacol. 1972 Jul;45(3):404–416. doi: 10.1111/j.1476-5381.1972.tb08097.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. HUKOVIC S., RAND M. J., VANOV S. OBSERVATIONS ON AN ISOLATED, INNERVATED PREPARATION OF RAT URINARY BLADDER. Br J Pharmacol Chemother. 1965 Feb;24:178–188. doi: 10.1111/j.1476-5381.1965.tb02093.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ichida S., Oka H., Masada A., Fujisue T., Hata T., Matsuda N. Effects of synthetic omega-conotoxin on the contractile responses of segments of rat ileum, stomach fundus and uterus and guinea pig taenia coli. Jpn J Pharmacol. 1988 Dec;48(4):395–405. doi: 10.1254/jjp.48.395. [DOI] [PubMed] [Google Scholar]
  15. Keith R. A., Mangano T. J., Pacheco M. A., Salama A. I. Characterization of the effects of omega-conotoxin GVIA on the responses of voltage-sensitive calcium channels. J Auton Pharmacol. 1989 Aug;9(4):243–252. doi: 10.1111/j.1474-8673.1989.tb00215.x. [DOI] [PubMed] [Google Scholar]
  16. Kerr L. M., Yoshikami D. A venom peptide with a novel presynaptic blocking action. Nature. 1984 Mar 15;308(5956):282–284. doi: 10.1038/308282a0. [DOI] [PubMed] [Google Scholar]
  17. Lefebvre R. A. Study on the possible neurotransmitter of the non-adrenergic non-cholinergic innervation of the rat gastric fundus. Arch Int Pharmacodyn Ther. 1986 Apr;280(2 Suppl):110–136. [PubMed] [Google Scholar]
  18. Li C. G., Majewski H., Rand M. J. Facilitation of noradrenaline release from sympathetic nerves in rat anococcygeus muscle by activation of prejunctional beta-adrenoceptors and angiotensin receptors. Br J Pharmacol. 1988 Oct;95(2):385–392. doi: 10.1111/j.1476-5381.1988.tb11657.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Li C. G., Rand M. J. Evidence for a role of nitric oxide in the neurotransmitter system mediating relaxation of the rat anococcygeus muscle. Clin Exp Pharmacol Physiol. 1989 Dec;16(12):933–938. doi: 10.1111/j.1440-1681.1989.tb02404.x. [DOI] [PubMed] [Google Scholar]
  20. Li C. G., Rand M. J. Prejunctional inhibition of non-adrenergic non-cholinergic transmission in the rat anococcygeus muscle. Eur J Pharmacol. 1989 Sep 1;168(1):107–110. doi: 10.1016/0014-2999(89)90640-7. [DOI] [PubMed] [Google Scholar]
  21. Lundy P. M., Frew R. Evidence of omega-conotoxin GV1A-sensitive Ca2+ channels in mammalian peripheral nerve terminals. Eur J Pharmacol. 1988 Nov 8;156(3):325–330. doi: 10.1016/0014-2999(88)90277-4. [DOI] [PubMed] [Google Scholar]
  22. Maggi C. A., Patacchini R., Giuliani S., Santicioli P., Meli A. Evidence for two independent modes of activation of the 'efferent' function of capsaicin-sensitive nerves. Eur J Pharmacol. 1988 Nov 8;156(3):367–373. doi: 10.1016/0014-2999(88)90282-8. [DOI] [PubMed] [Google Scholar]
  23. Maggi C. A., Patacchini R., Santicioli P., Lippe I. T., Giuliani S., Geppetti P., Del Bianco E., Selleri S., Meli A. The effect of omega conotoxin GVIA, a peptide modulator of the N-type voltage sensitive calcium channels, on motor responses produced by activation of efferent and sensory nerves in mammalian smooth muscle. Naunyn Schmiedebergs Arch Pharmacol. 1988 Aug;338(2):107–113. doi: 10.1007/BF00174856. [DOI] [PubMed] [Google Scholar]
  24. McCulloch M. W., Papanicolaou M., Rand M. J. Evidence for autoinhibition of stimulation-induced noradrenaline release from vasa deferentia of the guinea-pig and rat. Br J Pharmacol. 1985 Oct;86(2):455–464. doi: 10.1111/j.1476-5381.1985.tb08915.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. McGrath J. C. Adrenergic and 'non-adrenergic' components in the contractile response of the vas deferens to a single indirect stimulus. J Physiol. 1978 Oct;283:23–39. doi: 10.1113/jphysiol.1978.sp012486. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Miller R. J. Multiple calcium channels and neuronal function. Science. 1987 Jan 2;235(4784):46–52. doi: 10.1126/science.2432656. [DOI] [PubMed] [Google Scholar]
  27. Oyama Y., Tsuda Y., Sakakibara S., Akaike N. Synthetic omega-conotoxin: a potent calcium channel blocking neurotoxin. Brain Res. 1987 Oct 20;424(1):58–64. doi: 10.1016/0006-8993(87)91192-9. [DOI] [PubMed] [Google Scholar]
  28. Sano K., Enomoto K., Maeno T. Effects of synthetic omega-conotoxin, a new type Ca2+ antagonist, on frog and mouse neuromuscular transmission. Eur J Pharmacol. 1987 Sep 11;141(2):235–241. doi: 10.1016/0014-2999(87)90268-8. [DOI] [PubMed] [Google Scholar]
  29. Sneddon P., Westfall D. P. Pharmacological evidence that adenosine triphosphate and noradrenaline are co-transmitters in the guinea-pig vas deferens. J Physiol. 1984 Feb;347:561–580. doi: 10.1113/jphysiol.1984.sp015083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tsien R. W., Lipscombe D., Madison D. V., Bley K. R., Fox A. P. Multiple types of neuronal calcium channels and their selective modulation. Trends Neurosci. 1988 Oct;11(10):431–438. doi: 10.1016/0166-2236(88)90194-4. [DOI] [PubMed] [Google Scholar]
  31. VANE J. R. A sensitive method for the assay of 5-hydroxytryptamine. Br J Pharmacol Chemother. 1957 Sep;12(3):344–349. doi: 10.1111/j.1476-5381.1957.tb00146.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wong-Dusting H. K., Rand M. J. Pre- and postjunctional effects of neuropeptide Y on the rabbit isolated ear artery. Clin Exp Pharmacol Physiol. 1988 May;15(5):411–418. doi: 10.1111/j.1440-1681.1988.tb01094.x. [DOI] [PubMed] [Google Scholar]
  33. Wong-Dusting H. K., Reid J. J., Rand M. J. Paradoxical effects of endothelin on cardiovascular noradrenergic neurotransmission. Clin Exp Pharmacol Physiol. 1989 Apr;16(4):229–233. doi: 10.1111/j.1440-1681.1989.tb01548.x. [DOI] [PubMed] [Google Scholar]
  34. el-Din M. M., Malik K. U. Differential effect of omega-conotoxin on release of the adrenergic transmitter and the vasoconstrictor response to noradrenaline in the rat isolated kidney. Br J Pharmacol. 1988 Jun;94(2):355–362. doi: 10.1111/j.1476-5381.1988.tb11537.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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