Research reportThe role of 5-HT1A receptors in control of lower urinary tract function in cats
Introduction
Various studies have implicated serotonin (5-hydroxytryptamine, 5-HT) in control of lower urinary tract function. 5-HT terminals and various receptor subtypes are intimately associated with spinal cord areas that contain afferent and efferent components of lower urinary tract neural control centers [3], [15], [18], [27], [37]. Pharmacological and physiological studies have indicated that the serotonergic system influences neural control of lower urinary tract function [6], [11], [13], [19], [21], [30], [32], [36].
One receptor subtype that appears to be particularly localized to spinal cord regions that subserve lower urinary tract function is the 5-HT1A receptor subtype [37]. In both rat and cat, this receptor subtype shows moderate to dense binding in areas of the dorsal horn that contain bladder afferent terminals [24], [26], in the sacral parasympathetic nucleus, which contains efferent innervation of the bladder [23], [26], and in rat and cat homologs of Onuf’s nucleus, which contain urethral sphincter motor neurons [20], [35].
Pharmacological studies of 5-HT1A receptor activation in rats showed that 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), the prototypical 5-HT1A receptor agonist [16], [22], produced a micturition contraction when bladder volume was just subthreshold for producing a physiological bladder contraction [19]. This implied that 5-HT1A receptor activation facilitates bladder activity in the rat. However, in cats [36], 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), a non-selective 5-HT1A receptor agonist, inhibited bladder activity.
Thus, the current study was undertaken to more precisely define the role of 5-HT1A receptors in regulation of bladder function in the cat and to determine its effects on external urethral sphincter activity using more selective 5-HT1A receptor agonists and antagonists. Additionally, the effects of the drugs were examined under conditions of bladder irritation.
Section snippets
Methods
Transvesical cystometrograms (CMG) were performed as previously described in detail [32]. Briefly, 19 adult female cats were anesthetized with α-chloralose (50–75 mg/kg i.v., Sigma, St. Louis, MO, USA). Following a midline laparotomy, the bladder was cannulated through the dome to allow infusion of fluids and recording of intravesical pressure. The urethra remained patent to allow expulsion of fluids during reflex micturition. In five animals, CMGs were recorded by emptying the bladder,
Results
Under control conditions (Fig. 1A), large (30–50 cm H2O), rapid increases in intravesical pressure (i.e. micturition contractions) were recorded after infusion of approximately 5 ml saline into an initially empty bladder. Upon switching to infusion of acetic acid (Fig. 1B), bladder capacity, contraction amplitude, and contraction duration were reduced, while the contraction frequency was increased as previously reported [32]. Very little peri-urethral EMG activity was recorded during infusion
Discussion
The present study has shown that 5-HT1A receptor activation inhibits bladder activity (i.e. decrease in contraction frequency and increase in capacity) and facilitates EUS EMG activity under conditions of acetic acid infusion into the bladder. 8-OH-DPAT is a fairly selective 5-HT1A receptor agonist, while 5-MeODMT is less selective [16], [22]. However, since the effects of both agonists were blocked by two selective 5-HT1A receptor antagonists [12], [16], the results strongly suggest that the
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