Functional studies on the cholinergic and sympathetic innervation of the rat proximal urethra: effect of pelvic ganglionectomy or experimental diabetes.

1. Isolated rings of rat proximal urethra contracted in response to acetylcholine, noradrenaline, phenylephrine, tachykinins or field stimulation. In the presence of field stimulation-induced contractions, isoprenaline or CGRP produced an inhibitory effect on evoked contractions. 2. Electrical field stimulation produced frequency-related contractions which, when using trains of stimuli, consisted of a phasic and a tonic response. These contractions were abolished by tetrodotoxin (1 microM) but unaffected by hexamethonium (10 microM). 3. Atropine (3 microM) produced a partial inhibition of these nerve-mediated contractions, slightly more evident on the tonic than the phasic response. In the presence of atropine (3 microM), phentolamine (3 microM) or prazosin (1-10 nM) produced an almost complete inhibition of the response to field stimulation. 4. After bilateral removal of the pelvic ganglia, electrical field stimulation was still able to induce tetrodotoxin-sensitive contractions of the rat proximal urethra. However, the inhibitory effect of atropine was much reduced as compared to controls, while the phentolamine-sensitive portion of the response was increased. 5. DMPP (0.1 mM) a nicotinic receptor agonist, produced a contraction (phasic and tonic components) which was strongly inhibited by hexamethonium (10 microM), abolished by prazosin (1 microM) and reduced by tetrodotoxin (3 microM). 6. In urethral rings from diabetic rats (i.v. streptozotocin 7-9 weeks before) the contractile response to acetylcholine or noradrenaline as well as the response to field stimulation were unchanged as compared to controls. 7. Capsaicin (1 microM) produced an inhibitory effect on the nerve-mediated contractions of the rat proximal urethra. This response was abolished by pelvic ganglionectomy but was unaffected in streptozotocin-treated rats. 8. These findings provide functional evidence that both cholinergic and noradrenergic nerves mediate the contractions of the rat proximal urethra. In addition, capsaicin-sensitive sensory nerves can produce certain local motor responses through release of endogenous neuropeptides. In vivo studies are needed to examine the interplay between these differents sets of motor nerves in the regulation of proximal urethra motility.