EFFECTS OF OMEGA-CONOTOXIN ON ADRENERGIC, CHOLINERGIC AND NANC NEUROTRANSMISSION IN THE RABBIT URETHRA AND DETRUSOR

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-conotoxin-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.