Action Mechanisms Involved in the Effect of Non-peptide Opioid Delta-receptor Agonist and Antagonist on the Micturition Reflex in the Rat

• Main Authors: WANG, Y. C., 王奕棋
• Other Authors: FU, T. C.
• Format: Others
• Language: zh-TW
• Published: 2000
• Online Access: http://ndltd.ncl.edu.tw/handle/98791048854741950130

碩士 === 國立臺灣大學 === 生理學研究所 === 88 === Morphine and a number of other opioid analgesics produce urinary retention in clinical use. This action appears to involve the activation of delta and mu opioid receptors in both supraspinal and spinal levels. Thus, Pharmacologic manipulation of endogenous opioid mechanisms may be clinically useful in treating neurogenic bladder dysfunction, such as urinary incontinence. The purpose of this study is to investigate the action mechanisms of two non-peptide opioid delta-receptor-selective agonists (SNC-80, BW373U86) and an antagonist (naltrindole) involved in the micturition reflex. They were tested by the spontaneous volume-induced contraction of the urinary bladder in the urethane-anesthetized rats. The intravesical pressure, the pelvic afferent activity (PANA) and efferent activities (PENA) as well as the EMG of external urethral sphincter (EUS-EMG) were recorded simultaneously. The intracerebroventricular administration of SNC-80 or BW373U86 caused inhibition of the micturition reflex, and BW373U86 also induced a reduction in peak micturition pressure (PMP) and EUS-EMG. The intrathecal infusion of SNC-80 or BW373U86 produced a complete short-lasting inhibition of micturition reflex. The inhibition of the EUS-EMG, PANA and PENA were persisted when the micturition reappeared. On the other hand, the intracerebroventricular administration of naltrindole, the micturition reflex was facilitated but the PMP was inhibited. Whereas intrathecal infusion of naltrindole produced a series of ineffective bladder contractions before the first micturition started. In local application of SNC-80 or BW373U86, however, the micturition interval, PMP, EUS-EMG, PANA, and PENA were all inhibited. Local application of naltrindole produced the effects just opposite to the agonist stated above, except the PMP, which was reduced in a high dose. The opioid delta receptor agonists and antagonist at the supraspinal site failed to alter the pelvic nerve activity suggest that supraspinal endogenous opioid system does not act directly on the sacral preganglionic neurons, but indirectly through descending fibers on the interneuron at the level of afferent inputs in the sacral spinal cord. However, these agonists at the spinal site may cause direct inhibition of the sacral preganglionic neuron discharge, and then inhibit the pelvic nerve activity. These results indicate that the brain endogenous opioid system seems to play a major role in the modulation of the micturition threshold and the frequency, whereas in the spinal region, enkephalinergic neurons seem to control the activity of sacral preganglionic neurons. It is concluded that the opioid d-receptor agonist, SNC-80, but not BW373U86, may be a good candidate for the treatment of the patient with urinary incontinence.