Biomedical subjects

M J Espey

Publications and source records attributed to M J Espey.

6 recordsLinked to original sources

PubMed1998

Serotonergic modulation of spinal ascending activity and sacral reflex activity evoked by pelvic nerve stimulation in cats.

Serotonin (5-HT) may be inhibitory to micturition at a spinal level. A potential mechanism of action for serotonergic inhibition of bladder function is a depression of the ascending limb of the supraspinal reflex mediating micturition. Ascending activity evoked by pelvic nerve stimulation was recorded in the thoracic spinal cord of anesthetized cats. For comparison, spinal reflex activity evoked by pelvic nerve stimulation was recorded on the pudendal nerve. The effects of intrathecal administration of serotonergic agents were examined to determine whether spinal and supraspinal responses to bladder afferent activation were modulated by 5-HT. Methysergide (60 nmol), a non-selective serotonergic antagonist, increased ascending activity by 61+/-7% and depressed spinal reflex activity by 38+/-6%. Zatosetron (10 nmol), a 5-HT3 antagonist had a similar effect on both activities (increased by 93+/-24% and decreased by 77+/-7%, respectively). The effect on ascending activity of blocking 5-HT3 receptors was also confirmed with ICS 205930 and MDL 72222. 2-Methyl-5-HT (800 nmol), a 5-HT3 agonist, depressed ascending activity to 46+/-9% of control, but enhanced spinal reflex activity by 73+/-92%. These results demonstrate that stimulation of 5-HT3 and methysergide-sensitive 5-HT receptors can inhibit ascending activity and facilitate spinal reflex activity elicited by activation of bladder afferents. It is suggested that descending serotonergic pathways may participate in the spinal coordination of urinary continence.

Afferent Pathways↗

PubMed1998

Evidence for a strychnine-sensitive mechanism and glycine receptors involved in the control of urethral sphincter activity during micturition in the cat.

Micturition in the decerebrate cat is characterized by a coordinated bladder contraction and a simultaneous decrease in external urethral sphincter (EUS) efferent activity. Without the suppression of EUS activity, voiding is significantly impaired, resulting in a state sometimes referred to as bladder-sphincter dyssynergia. The aim of the present study was to determine whether glycinergic inhibition contributes to the suppression of EUS activity during micturition evoked by bladder distension or electrical stimulation of the pontine micturition center (PMC) in decerebrate cats. Using subconvulsive intravenous doses of strychnine (0.1-0.24 mg/kg), we examined changes in bladder and EUS electroneurographic (ENG) activity during micturition. Following subconvulsive doses of strychnine, tonic EUS ENG activity increased during bladder filling in five of six animals. In the presence of strychnine, it was possible to evoke reflex bladder contractions of similar duration and peak pressure to those observed before strychnine administration. However, there was an absence of suppression of EUS ENG activity during the bladder contractions in all the animals. To determine whether the changes in sphincter activity could be due to strychnine acting at glycine receptors on EUS motoneurons, sacral spinal tissue was processed for a structural protein (gephyrin) associated with the glycine receptor. Motoneurons in Onufs nucleus in S1 were identified using choline acetyltransferase immunohistochemistry and subsequently processed with a gephyrin monoclonal antibody. Abundant gephyrin labeling was evident throughout Onufs nucleus. Since Onufs nucleus is made up of EUS and other motoneuron populations, a sample of antidromically identified urethral and anal sphincter motoneurons were intracellularly labeled with tetramethylrhodamine dextran (TMR-D) and then processed with the gephyrin antibody. Using dual-beam confocal microscopy, gephyrin immunoreactivity was observed on the soma and proximal processes of individual EUS motoneurons in both male and female animals. It was concluded that a strychnine-sensitive mechanism contributes to the suppression of sphincter activity normally observed during voiding. Although glycinergic inhibition may affect several components of the circuitry responsible for micturition, it appears that the suppression of EUS motoneurons during micturition may be partly due to a direct glycinergic inhibition of the EUS motoneurons.

Animals↗

PubMed1995

Serotonergic modulation of cat bladder function before and after spinal transection.

Micturition was evoked in conscious cats by infusing saline into the bladder at a physiological rate. Drugs were administered intrathecally. Micturition volume threshold was increased by 5-hydroxytryptamine (5-HT, serotonin) and decreased by zatosetron, a 5-HT3 receptor antagonist, in spinally intact cats. Thus 5-HT3 receptors inhibit micturition. After complete spinal transection, serotonin reduced volume threshold in 3 of 4 cats, indicating an alteration in serotonergic control. However, 2-methyl-5-HT, a 5-HT3 receptor agonist, increased volume threshold. Thus 5-HT3 receptor-mediated inhibition of bladder function remains after spinal transection. We conclude that some, but not all, serotonergic modulation of bladder function is altered after spinal transection.

Animals↗

PubMed1992

Effect of 5-HT receptor and adrenoceptor antagonists on micturition in conscious cats.

Micturition was induced in awake cats by infusing saline into the bladder at a physiological filling rate. Methysergide, a serotonergic antagonist given intrathecally, decreased the volume at which micturition occurred. Phentolamine, a non-specific alpha-adrenoceptor antagonist, also decreased volume threshold. Prazosin, an alpha 1-adrenoceptor antagonist, was without effect on micturition. These results imply that 5-HT receptors and alpha 2-adrenoceptors may be inhibitory to micturition at a spinal level.

Adrenergic alpha-Antagonists↗

PubMed1991

Alpha 2-adrenoceptors not imidazole receptors mediate depression of a sacral spinal reflex in the cat.

In chloralose-anaesthesized cats, clonidine, an alpha 2-adrenoceptor agonist with an imidazole ring, depressed pudendal nerve reflex activity. Clonidine's inhibitory action on this compound action potential response was mimicked by guanabenz, a non-imidazole alpha 2-adrenoceptor agonist, and was reversed by SK & F 86466, a non-imidazole alpha 2-adrenoceptor antagonist. These results imply that clonidine's action on this reflex related to urinary sphincter function is mediated by alpha 2-adrenoceptors and is not dependent on an imidazole structure.

Action Potentials↗

PubMed1991

8-Phenyltheophylline reverses the antinociceptive action of morphine in the periaqueductal gray.

Morphine was injected into the periaqueductal gray region of the rat and 8-phenyltheophylline, an adenosine receptor antagonist, was injected intrathecally 15 or 30 min later, to determine whether supraspinally-administered morphine activated descending mechanisms to release adenosine (or a nucleotide which is metabolized to adenosine) from the spinal cord. 8-Phenyltheophylline (10 micrograms) reversed the antinociceptive action of morphine in the hot plate but not the tail-flick test. A combination of methysergide/phentolamine (15 micrograms each) reversed the action of morphine in both tests. 8-Phenyltheophylline retained the ability to reverse the action of morphine in the hot plate test in rats pretreated with 6-hydroxydopamine (to induce degeneration of descending noradrenergic pathways) but reversal was no longer observed in rats pretreated with 5,7-dihydroxytryptamine (after pretreatment with desipramine, to induce degeneration of descending serotonergic pathways). These results indicate that a component of the supraspinal antinociceptive action of morphine is due to release of adenosine or nucleotide, within the spinal cord and this release is dependent on intact serotonergic pathways.

5,7-Dihydroxytryptamine↗