Effects of ω‐conotoxin on adrenergic, cholinergic and NANC neurotransmission in the rabbit urethra and detrusor

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Abstract

The effects of ω‐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. 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 Nω‐nitro‐l‐arginine. ω‐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 ω‐conotoxin‐resistant relaxation in lamina propria, suggesting that neuronal L or T VOCCs were not involved in the response. EFS contracted urethral smooth muscle at resting tension. The contractions were virtually abolished by TTX or prazosin. ω‐Conotoxin effectively inhibited the contractile responses to EFS, but not those to exogenous noradrenaline. An ω‐conotoxin‐resistant contraction was, however, observed at high frequencies of stimulation. 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%. ω‐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). ω‐Conotoxin did not affect the contractile responses to carbachol or adenosine 5′‐triphosphate. 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 ω‐conotoxin. The adrenergic contraction in the urethra was 10 times and the cholinergic contraction in the detrusor was three times more sensitive to ω‐conotoxin than the NANC responses. These results suggest that NANC neurotransmission is less inhibited by ω‐conotoxin than transmission mediated by adrenergic and cholinergic nerves in the rabbit lower urinary tract. In the urethra a marked ω‐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. 1993 British Pharmacological Society

Detaljer

Författare
Enheter & grupper
Externa organisationer
  • Lund University
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Farmakologi och toxikologi

Nyckelord

Originalspråkengelska
Sidor (från-till)1285-1290
Antal sidor6
TidskriftBritish Journal of Pharmacology
Volym110
Utgivningsnummer4
StatusPublished - 1993 jan 1
PublikationskategoriForskning
Peer review utfördJa