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-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.(ABSTRACT TRUNCATED AT 250 WORDS)