Nociceptin and the micturition reflex (original) (raw)
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Multiple Sites of Action in the Inhibitory Effect of Nociceptin on the Micturition Reflex
The Journal of Urology, 2000
Purpose: Nociceptin, the endogenous peptide ligand for the opioid receptor-like 1 (ORL 1 ) receptors, exerts a naloxone-resistant suppressant effect on micturition reflex after intravenous administration. This work aims to elucidate the mechanism and the site of action of the inhibitory effect of nociceptin on the micturition reflex.
The inhibitory effect of nociceptin on the micturition reflex in anaesthetized rats
British Journal of Pharmacology, 1998
1 We have investigated the eect of nociceptin on the micturition re¯ex evoked by distension or topical application of capsaicin on the urinary bladder of urethane-anaesthetized rats. 2 Nociceptin produced a dose-dependent (3 ± 100 nmol kg 71 i.v.) transient suppression of the distension-evoked micturition re¯ex: its eect was not modi®ed by guanethidine (68 mmol kg 71 s.c.) nor by bilateral cervical vagotomy, alone or in combination, and by naloxone (1.2 mmol kg 71 i.v.). 3 Nociceptin (100 nmol/kg i.v.) slightly (about 30%) inhibited the contractions of the rat bladder produced by pre-or postganglionic electrical stimulation of the pelvic nerve. 4 Nociceptin almost totally abolished the re¯ex component of the response to topical capsaicin (1 mg in 50 ml). 5 In the rat isolated bladder, submaximal contractions produced by electrical ®eld stimulation were slightly reduced (25+4% inhibition) by 1 mM nociceptin. Nociceptin did not aect the contraction of the rat bladder induced by acetylcholine (10 mM) or ATP (1 mM). 6 These ®ndings indicate that nociceptin exerts a naloxone-resistant suppression of the volume-evoked micturition re¯ex which involves inhibition of transmitter release from postganglionic bladder nerves. An inhibitory eect on bladder aerent nerves is also suggested.
Antitussive action of nociceptin in the cat
European Journal of Pharmacology, 2001
Experiments were conducted to determine the influence of the specific ORL1 receptor agonist, nociceptin, on the cough reflex in the cat. Cats were anesthetized and allowed to breathe spontaneously. Cough was elicited by mechanical stimulation of the intrathoracic Ž y1 . airway. Intravenous administration of nociceptin 0.001-3.0 mg kg inhibited cough number and the magnitude of abdominal muscle Ž . electromyogram EMG discharge during cough in a dose-dependent manner. Nociceptin had no effect on the magnitude of the inspiratory muscle EMG during cough. These effects of nociceptin were antagonized by pretreatment with the ORL1 receptor antagonist, wŽ .
Evidence for a role of tachykinins as sensory transmitters in the activation of micturition reflex
Neuroscience, 1993
The possible involvement of tachykinin neurokinin-1 and neurokinin-2 receptors in the activation of various micturition-related reflexes was assessed by the intrathecal administration of selective neurokinin-1 or neurokinin-2 receptor antagonists at lumbosacral spinal cord level in urethane-anaesthetized rats. The effect of the glutamate N-methyl-D-aspartate receptor antagonist, 2-amino-5-phosphonovaleric acid, was also investigated for comparison. The effect of antagonists was investigated on: (i) the chemonociceptive vesicovesical reflex activated by topical application of capsaicin onto the urinary bladder; (ii) the distension-induced micturition reflex produced by transvesical filling with saline; (iii) distension-induced rhythmic bladder contractions in isovolumetric conditions (urethra-ligated rats); and (iv) the somatovesical excitatory reflex caused by noxious perineal pinching. The neurokinin-2
Tachykinins as modulators of the micturition reflex in the central and peripheral nervous system
Regulatory Peptides, 2001
Ž . In the normal urinary bladder, tachykinins TKs are expressed in a population of bladder nociceptors that is sensitive to the excitatory Ž Ž . . and desensitizing effects of capsaicin i.e., capsaicin-sensitive primary afferent neurons CSPANs . Several endobiotics or xenobiotics excite CSPANs and release TKs and other mediators at both the peripheral and spinal cord level. The peripheral release of TKs Ž . determines a set of responses known as neurogenic inflammation that includes vasodilatation, plasma protein extravasation, smooth muscle contraction and stimulation of afferent nerves. Following chronic inflammation, both immune cells and capsaicin-resistant sensory neurons can de novo express TKs: whether these pools of TKs are releasable and contribute to inflammatory processes is presently unsettled. At the spinal cord level, the release of TKs contributes in determining an altered pattern of vesicourethral reflexes in response Ž . Ž . to nociceptive stimulation of the bladder by conveying: a the afferent transmission to supraspinal sites, and b descending or sensory Ž . inputs to the sacral parasympathetic nucleus SPN . Recent evidence also attribute a synergetic role of TKs in the supraspinal modulation of the sensory arm of the micturition reflex.
Nociceptin and neurotransmitter release in the periphery
Peptides, 2000
Nociceptin exerts a general modulatory effect on transmitter release from sympathetic, parasympathetic, NANC and sensory nerve endings in the peripheral nervous system in various species. This effect occurs at a prejunctional level and is independent from the activation of , ␦ and opioid receptors. Despite the growing evidence describing the peripheral activity of nociceptin since its discovery in 1995, the lack of selective and potent antagonists does not allow us to draw conclusions on the putative physiological role of this peptide at this level.
Autonomic Neuroscience, 2000
Mesenteric nerve stimulation (MNS) in the presence of guanethidine and hexamethonium antidromically stimulated extrinsic sensory nerve fibers and cholinergic myenteric motor neurons, resulting in longitudinal muscle contraction in the isolated guinea-pig ileum. Nociceptin (NC) is a recently discovered neuropeptide that structurally resembles an opioid peptide. The aim of the current study was to examine how NC affects the contractile responses to MNS in the isolated guinea-pig ileum, in comparison with an opiate, methionine-enkephalin. These contractions were auxotonically recorded and their amplitude was analyzed. NC (1-100 nM) and methionine-enkephalin (0.1-10 mM) concentration-dependently inhibited the response to MNS (20 Hz, 0.5 ms, supramaximal currents). Naloxone (10 mM) significantly diminished the inhibitory effect of methionine-enkephalin (0.1-10 mM), but did not antagonize the inhibitory effect of NC (1-100 nM). We conclude that NC receptors, distinct from opioid receptors, exist on the capsaicin-sensitive sensory nerve fibers and / or myenteric cholinergic motor neurons in the guinea-pig ileum and that specific antagonists for these NC receptors are not found yet.