Inhibition of noradrenaline release by omega-conotoxin GVIA in the rat tail artery

Br J Pharmacol. 1989 Jan;96(1):101-10. doi: 10.1111/j.1476-5381.1989.tb11789.x.

Abstract

1. The perivascular nerves of isolated tail arteries from Wistar rats were stimulated with field pulses (1 Hz, 2 pulses, every 2 min). omega-Conotoxin 10 nmol l-1 depressed neurogenically mediated contractions, but did not influence the contractions to noradrenaline 0.1-0.3 mumol l-1. 2. The inhibitory effect of omega-conotoxin was concentration-dependent (IC50 = 3.8 nmol l-1). It did not reach a steady-state during 30 min incubation and could not be reversed upon subsequent washout for another 60 min. 3. A gradual increase in the Ca2+ concentration of the medium from 1.25 mmol l-1 to 10 mmol l-1 enhanced vasoconstriction and attenuated the action of omega-conotoxin 10 nmol l-1. When a low stimulation intensity (120 mA) was used at high external Ca2+ (10 mmol l-1), similar contractile responses were obtained as under normal conditions (200 mA current, 2.5 mmol l-1 Ca2+). However, the inverse relationship between the effect of the toxin and external Ca2+ remained unchanged. 4. The time-course and degree of the inhibition by omega-conotoxin 3 nmol l-1 was identical in tail arteries of spontaneously hypertensive rats (SHR) and their normotensive controls (WKY). 5. When tail arteries of Wistar rats were preincubated with [3H]-noradrenaline, field stimulation (0.4 Hz, 24 pulses, every 16 min) evoked tritium overflow and vasoconstriction. omega-Conotoxin 30 nmol l-1 inhibited both responses to a similar extent. 6. Our results suggest that omega-conotoxin selectively blocks Ca2+ channels in the terminals of perivascular nerves and thereby reduces the release, but not the contractile effect of the sympathetic transmitter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / pharmacology
  • Calcium Channel Blockers / toxicity*
  • Electric Stimulation
  • Male
  • Mollusk Venoms / toxicity*
  • Norepinephrine / metabolism*
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred Strains
  • Rats, Inbred WKY
  • Tail / blood supply*
  • Vasoconstriction / drug effects
  • omega-Conotoxin GVIA

Substances

  • Calcium Channel Blockers
  • Mollusk Venoms
  • omega-Conotoxin GVIA
  • Calcium
  • Norepinephrine