Effects of omega-conotoxin on adrenergic, cholinergic and NANC neurotransmission in the rabbit urethra and detrusor

Br J Pharmacol. 1993 Dec;110(4):1285-90. doi: 10.1111/j.1476-5381.1993.tb13957.x.

Abstract

1. The effects of omega-conotoxin GVIA (an inhibitor of N-type voltage-operated calcium channels; VOCCs) were compared on adrenergic, cholinergic and non-adrenergic, non-cholinergic (NANC) responses induced by electrical field stimulation (EFS) in the rabbit urethra and detrusor. 2. EFS induced a relaxation in urethral smooth muscle and lamina propria precontracted by arginine vasopressin (AVP). The relaxation was abolished by tetrodotoxin (TTX) or the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine. omega-Conotoxin inhibited the relaxation induced by EFS, but not that elicited by the NO donor 3-morpholino-sydnonimin. The inhibition, however, decreased with increasing frequencies of stimulation. Nimodipine, tetramethrin and nickel did not affect the omega-contoxin-resistant relaxation in lamina propria, suggesting that neuronal L or T VOCCs were not involved in the response. 3. EFS contracted urethral smooth muscle at resting tension. The contractions were virtually abolished by TTX or prazosin. omega-Conotoxin effectively inhibited the contractile responses to EFS, but not those to exogenous noradrenaline. An omega-conotoxin-resistant contraction was, however, observed at high frequencies of stimulation. 4. The detrusor responded with frequency-dependent contractions upon EFS. A TTX-resistant contraction less than 10% of controls remained at 30 Hz stimulation. At a stimulation frequency of 10 Hz, scopolamine reduced the EFS-induced contraction by 71%. omega-Conotoxin inhibited the responses in both the absence and presence of scopolamine. The inhibition decreased with increasing frequencies of stimulation (examined in the absence of scopolamine). omega-Conotoxin did not affect the contractile responses to carbachol or adenosine 5'-triphosphate. 5. The adrenergic contraction (25 Hz) and NANC relaxation (10 Hz) in the urethra, and cholinergic and NANC contractions (10 Hz) in the detrusor were inhibited concentration-dependently by omega-conotoxin.The adrenergic contraction in the urethra was 10 times and the cholinergic contraction in the detrusor was three times more sensitive to omega-conotoxin than the NANC responses.6. These results suggest that NANC neurotransmission is less inhibited by omega-conotoxin than transmission mediated by adrenergic and cholinergic nerves in the rabbit lower urinary tract. In the urethra a marked omega-conotoxin-resistant component of the NANC relaxation was observed which increased with increasing stimulation frequencies and was unaffected by inhibitors of L and T type VOCCs. This raises the question whether VOCCs of a type other than L, T, and N is involved in the mediation of this response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism*
  • Animals
  • Calcium Channel Blockers / pharmacology*
  • Dose-Response Relationship, Drug
  • Electric Stimulation
  • Female
  • In Vitro Techniques
  • Muscle Contraction / drug effects
  • Norepinephrine / metabolism*
  • Peptides / pharmacology*
  • Peripheral Nerves / drug effects*
  • Rabbits
  • Synaptic Transmission / drug effects*
  • Tetrodotoxin / pharmacology
  • Urethra / drug effects
  • Urethra / innervation
  • Urethra / physiology
  • Urinary Bladder / drug effects
  • Urinary Bladder / innervation
  • Urinary Bladder / physiology
  • omega-Conotoxin GVIA

Substances

  • Calcium Channel Blockers
  • Peptides
  • Tetrodotoxin
  • omega-Conotoxin GVIA
  • Acetylcholine
  • Norepinephrine