Does pharmacological activation of 5-HT_1A receptors improve urine flow rate in female rats?

Abstract

Chen SC, Hsieh TH, Fan WJ, Lai CH, Peng CW. Does pharmacological activation of 5-HT1A receptors improve urine flow rate in female rats? Am J Physiol Renal Physiol 311: F166 -F175, 2016. First published May 4, 2016 doi:10.1152/ajprenal.00469.2015.-The role of 5-HT1A receptors in regulating voiding functions remains unclear, particularly regarding the urine flow rate (UFR) during voiding. This study examined the effects of 5-HT1A receptors on regulating urethral functions in female rats and investigated underlying modulatory mechanisms. Intravesical pressure (IVP), external urethral sphincterelectromyography (EUS-EMG), and UFR were simultaneously recorded during continuous transvesical infusion to examine the effects of a 5-HT1A receptor agonist (8-OH-DPAT) and antagonist (WAY-100635) on bladder and urethral functions. In addition, this study evaluated the independent roles of urethral striated and smooth muscles in the UFR in rats after a neuromuscular blockade (NMB) treatment and bilateral hypogastric nerve transection. Our results revealed that 8-OH-DPAT significantly increased the maximal UFR but reduced the mean UFR. This discrepancy may be because 8-OH-DPAT markedly increased the maximal UFR during the initial segment of the flow duration and subsequently induced an approximately zero level of long oscillatory waves during the remaining flow duration. Thus the mean UFR was reduced because of the prolonged approximately zero level of the UFR. However, paralyzing the EUS with an NMB agent, 8-OH-DPAT, significantly increased the maximal and mean UFRs because the prolonged zero level of the oscillatory UFR did not continue. These results support the hypothesis that the increased UFR in female rats during voiding is due to the induction of urethral smooth muscle relaxation by 8-OH-DPAT. This paper provides a detailed understanding of the role of 5-HT 1A receptors in controlling the UFR in female rats. intravesical pressure; EUS-EMG; 8-OH-DPAT; WAY-100635; neuromuscular blockade THE PRIMARY FUNCTIONS OF THE lower urinary tract (LUT) are storage and periodic urine elimination. These functions require reciprocal coordination between the urinary bladder and urethra outlets, including the bladder neck, urethra, and external urethral sphincter (EUS). The urethra consists of smooth and striated muscle layers that are regulated by the following three peripheral nerve sets: sacral parasympathetic (pelvic nerves) and thoracolumbar sympathetic nerves (hypogastric nerves) that innervate urethral smooth muscles, and sacral somatic nerves (pudendal nerves) that innervate urethral striated muscles including the EUS and pelvic floor muscles.Receptors for serotonin [5-hydroxytryptamine (5-HT)] comprise 14 structurally different 5-HT receptors in mammalian species, including 7 subfamilies (5-HT 1 -5-HT 7 ) (28). Pharmacological studies in animals have indicated that the three sets of LUT nerve terminals contain numerous 5-HT receptor subfamilies. Specifically, 5-HT 1A receptors are vital to LUT functions (32). The effects of 5-HT...

Transsynaptic tracing to dissect supraspinal serotonergic input regulating the bladder reflex in rats

“…Particularly, administration of 5-HT 1A receptor agonists facilitates the void, while the receptor antagonists reverse these effects in intact and chronically spinalized rats. [19][20][21] It is assumed that the supraspinal pathway extend in the bilateral dorsolateral funiculus and finally innervate the intermediolateral cell column (IML), where the axon terminals make synapses with sympathetic or parasympathetic preganglionic neurons. Based on the present results, we now know the detailed origin of the serotonergic descending pathway.…”