Effect of omega-agatoxin-IVA on autonomic neurotransmission

Eur J Pharmacol. 1994 Aug 11;261(1-2):79-84. doi: 10.1016/0014-2999(94)90303-4.

Abstract

omega-Agatoxin-IVA, a peptide from the venom of the funnel-web spider Agelenopsis aperta and a P type Ca2+ channel inhibitor, was examined for effects on responses to nerve stimulation in isolated autonomic neuroeffector preparations from the rabbit, guinea-pig and rat. Ca(2+)-dependent, tetrodotoxin sensitive, noradrenergic excitatory responses of rabbit pulmonary artery, rat vas deferens, and anococcygeus muscles, and cholinergic guinea-pig myenteric plexus preparations (all highly sensitive to the N type Ca2+ channel inhibitor omega-conotoxin-GVIA) were unaffected by omega-agatoxin-IVA (100 nM). Similarly, the neurogenic response of rat bladder, which has cholinergic, and non-adrenergic non-cholinergic (NANC) excitatory components, and the NANC inhibitory response of rat jejunum (atropine 0.5 microM- and guanethidine 5.0 microM-treated), which are partially sensitive and insensitive to omega-conotoxin-GVIA, respectively, were unaffected by omega-agatoxin-IVA (100 nM). Neurogenic NANC inhibitory responses of the guinea-pig taenia caecum, and rat anococcygeus muscles (atropine- and guanethidine-treated, and tone raised with prostaglandin F2 alpha), were also insensitive to omega-agatoxin-IVA. These results suggest that P type Ca2+ channels, if present, play an insignificant role in supplying the Ca2+ necessary for neurotransmitter release in the peripheral autonomic nervous system.

MeSH terms

  • Animals
  • Autonomic Nervous System / drug effects*
  • Calcium Channel Blockers / pharmacology*
  • Dinoprost / pharmacology
  • Electric Stimulation
  • Guinea Pigs
  • In Vitro Techniques
  • Male
  • Muscle, Smooth, Vascular / drug effects
  • Myenteric Plexus / drug effects
  • Neuroeffector Junction / drug effects
  • Norepinephrine / physiology
  • Peptides / pharmacology
  • Rabbits
  • Rats
  • Rats, Sprague-Dawley
  • Spider Venoms / pharmacology*
  • Synaptic Transmission / drug effects*
  • omega-Agatoxin IVA
  • omega-Conotoxins*

Substances

  • Calcium Channel Blockers
  • Peptides
  • Spider Venoms
  • omega-Agatoxin IVA
  • omega-Conotoxins
  • Conus magus toxin
  • Dinoprost
  • Norepinephrine