Spinal 5‐HT₂ receptor‐mediated facilitation of pudendal nerve reflexes in the anaesthetized cat

Abstract

1 5-Hydroxytryptamine (5-HT) is intimately associated with central sympathetic and somatic control of the lower urinary tract. The sympathetic and somatic innervation of the lower urinary tract is conveyed through efferent axons of the hypogastric and pudendal nerves, respectively. 2 The present study examined the effects of 2,5-dimethoxy-4-iodophenylisopropylamine (DOI), a 5-HT2 receptor subtype-selective agonist, on evoked potentials recorded from the central ends of the hypogastric and pudendal nerves in response to electrical stimulation of afferent fibres in the pelvic and pudendal nerves, respectively. Various spinalization paradigms were employed to localize the site of action. All cats were pretreated with xylamidine (1 mg kg-'), a peripherally-restricted 5-HT2 receptor antagonist. 3 In acute spinal cats, DOI (0.01-3 mg kg', i.v.) reliably produced dose-dependent increases in the pudendal nerve reflex (to 228+31 % of control). These increases were reversed by the 5-HT2 receptorselective antagonist, LY53857 (0.3-3 mg kg-', i.v.). On the other hand, in spinally-intact cats, DOI produced no significant changes in the pudendal reflex. However, within minutes of spinalization of DOI-pretreated cats, a marked increase (to 221+16% of control) in the pudendal reflex was observed which could be reversed by LY53857. No significant effects were observed on hypogastric reflexes in either acute spinal or spinally-intact cats following DOI administration. No effects were seen in either spinally-intact or acute spinal animals when LY53857 was administered as the initial drug. 4 These results indicate that activation of spinal 5-HT2 receptors facilitates pudendal reflexes. In spinally-intact cats, it is hypothesized that DOI activates supraspinal pathways that mediate inhibition of the pudendal reflexes and counteracts the facilitatory effects of spinal 5-HT2 receptor activation.

External Urethral Sphincter Motoneuron Properties in Adult Female Rats Studied In Vitro

“…EUS motoneurons also express PICs and appear to have comparable neuromodulatory influences (Burgard et al 2008;Paroschy and Shefchyk 2000;Rajaofetra et al 1992;Thor et al 1993;Ye et al 2009). In vivo studies of lower urinary tract function show that drugs that interact with these neuromodulatory influences alter EUS activity (Danuser and Thor 1996;de Groat et al 1990;Mbaki and Ramage 2008;Thor and Katofiasc 1995;Thor et al 2002). These observations are consistent with PICs having a role in EUS motoneuron firing behavior during urinary function.…”

Role of 5-HT1A receptors in control of lower urinary tract function in anesthetized rats

“…A similar interaction between glutamatergic transmission and monoaminergic modulatory mechanisms has been proposed to explain the reflex control of the EUS motoneurons and the action of duloxetine in the cat spinal cord (7,33,35), although in this species 5-HT 2 rather than 5-HT 1A receptors are thought to be involved (8,33). The clinical efficacy of duloxetine to enhance EUS function and reduce stress urinary incontinence (33) suggests that monoaminergic-glutamatergic interactions may be important for promoting urinary continence in humans.…”

Role of spinal serotonergic pathways in sneeze-induced urethral continence reflex in rats

“…5-HT enhances the guarding reflex by binding to 5-HT 2 receptors in rats and cats (8,24). Autoradiographic staining of spinal cord sections revealed high density of 5-HT 2 receptors in Onuf's nucleus but few receptors in the surrounding ventral horn (25).…”

“…Moreover, 5-HT receptors are divided into seven families (5-HT 1-7 ) (24). Among them, it is well-known that 5-HT 2 receptor stimulation activates the pudendal nerve to increase external urethral sphincter activity in cats, guinea pigs, and rats (8,9,24). It has also been reported that 5-HT 1A receptor activation can enhance external urethral sphincter activity in rats and cats (6,7,27).…”