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Titolo:
EFFECTS OF KAPPA-OPIOID RECEPTOR-SELECTIVE AGONISTS ON RESPONSES OF PELVIC NERVE AFFERENTS TO NOXIOUS COLORECTAL DISTENSION
Autore:
SU X; SENGUPTA JN; GEBHART GF;
Indirizzi:
UNIV IOWA,COLL MED,DEPT PHARMACOL,BOWEN SCI BLDG IOWA CITY IA 52242
Titolo Testata:
Journal of neurophysiology
fascicolo: 2, volume: 78, anno: 1997,
pagine: 1003 - 1012
SICI:
0022-3077(1997)78:2<1003:EOKRAO>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
GUINEA-PIG BRAIN; ADMINISTERED NOR-BINALTORPHIMINE; MYELINATED PRIMARY AFFERENTS; SACRAL SPINAL-CORD; URINARY-BLADDER; BINDING-SITES; MEDIATED ANTINOCICEPTION; RAT-BRAIN; NALOXONE BENZOYLHYDRAZONE; D-PEN(5) ENKEPHALIN;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
55
Recensione:
Indirizzi per estratti:
Citazione:
X. Su et al., "EFFECTS OF KAPPA-OPIOID RECEPTOR-SELECTIVE AGONISTS ON RESPONSES OF PELVIC NERVE AFFERENTS TO NOXIOUS COLORECTAL DISTENSION", Journal of neurophysiology, 78(2), 1997, pp. 1003-1012

Abstract

The aim of this study was to examine the effects of K-opioid receptorselective agonists on responses of mechanosensitive afferent fibers in the pelvic nerve. Single-fiber recordings were made from pelvic nerve afferents in the decentralized S1 dorsal root of the rat. A total of572 afferent fibers in the S1 dorsal root were identified by electrical stimulation of the pelvic nerve; 252 (44%) responded to noxious colorectal distension (CRD; 80 mmHg). Of these 252 fibers that responded to CRD, 100 were studied further. All 100 fibers gave monotonic increases in firing to increasing pressures of CRD. Eighty-eight fibers had low thresholds for response (mean: 3 mmHg) and 12 fibers had high-thresholds for response (mean: 28 mmHg). Responses of 17 fibers also were tested after instillation of 5% mustard oil (MO) into the colon. The resting activity of 16/17 fibers significantly increased after MO instillation; 13 (77%) also exhibited sensitization of responses to graded CRD when tested 30 min after intracolonic MO instillation. The effectsof kappa(1)-opioid receptor preferring agonists (U50,488H, U69,593 and U62,066), the K-2-opioid receptor preferring agonist bremazocine, and the kappa(3)-opioid receptor preferring agonist naloxone benzoylhydrazone (nalBzoH) were tested on responses of 64 mechanosensitive afferent fibers to noxious CRD. All five agonists dose-dependently inhibitedafferent fiber responses to noxious CRD. Doses producing inhibition to 50% of the control response to CRD did not differ among the five agonists, ranging from similar to 4 to 15 mg/kg. The effects of kappa(1),kappa(2), and kappa(3) receptor agonists were attenuated by naloxone;two kappa-opioid receptor-selective antagonists were ineffective. There were no differences in the dose-response relationships of these drugs for fibers recorded from untreated and irritant-treated colons. Conduction velocities of the fibers remained unaffected after high doses of all tested agonists. In an in vitro study, U50,488 (10(-4) M) did not produce any significant change in the tension of colonic smooth muscle. These results document that responses of mechanosensitive pelvic nerve afferent fibers innervating the colon are inhibited by kappa-opioid receptor agonists having varying affinities for putative kappa-opioid receptor subtypes. The inhibitory effects of these drugs likely are mediated by an action at receptors associated with the afferent fibers. The receptor at which these effects are produced is K-opioid-like but clearly different from the kappa-opioid receptor characterized in the CNS and is perhaps an orphan receptor.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/07/20 alle ore 22:59:12