Antagonism by SR 48692 of mechanical responses to neurotensin in rat intestine

被引：16

作者：

Mule, F

Serio, R

Postorino, A

Vetri, T

Bonvissuto, F

机构：

[1] Dipto. Biol. Cell. e dello Sviluppo, Laboratorio di Fisiologia Generale, Università di Palermo, 90128-Palermo, Viale delle Sci., Parco d'Orleans II

来源：

BRITISH JOURNAL OF PHARMACOLOGY | 1996年 / 117卷 / 03期

关键词：

neurotensin; neurotensin receptors; SR; 48692; non-peptide neurotensin antagonist; neurotensin intestinal effects;

D O I：

10.1111/j.1476-5381.1996.tb15216.x

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

1 The effects of SR 48692 on neurotensin (NT)-induced mechanical responses were investigated in rat duodenum and proximal colon by use of isometric, isovolumic preparations. 2 SR 48692 inhibited the relaxant responses to NT in duodenal circular and longitudinal muscle. It also antagonized the NT-induced contractile effects in duodenal circular muscle and in proximal colon (both muscular layers). 3 From Schild analysis the pA(2) value for SR 48692 was 8.2 in tissues where NT induced relaxant effects and 7.5 in tissues where NT induced contractile effects and the slope of the regression line was not significantly different from unity, indicating competitive antagonism. 4 SR 48692 did not antagonize the duodenal relaxant effect induced by noradrenaline and the contractile response to carbachol or substance P in duodenum and colon. 5 Our results demonstrate that SR 48692 selectively antagonizes the mechanical actions of NT in rat intestine and confirm the existence of specific NT receptors. Receptors that subserve a relaxant effect seem to be related, but not identical, to those that mediate contractile effects.

引用

页码：488 / 492

页数：5

共 24 条

[1] EFFECTS OF NEUROTENSIN AND NEUROTENSIN ANALOGS ON THE MIGRATING MYOELECTRICAL COMPLEXES IN THE SMALL-INTESTINE OF RATS [J].

ALSAFFAR, A ;

ROSELL, S .

ACTA PHYSIOLOGICA SCANDINAVICA, 1981, 112 (02) :203-208

[2] SOME QUANTITATIVE USES OF DRUG ANTAGONISTS [J].

ARUNLAKSHANA, O ;

SCHILD, HO .

BRITISH JOURNAL OF PHARMACOLOGY AND CHEMOTHERAPY, 1959, 14 (01) :48-58

[3] PHYSIOLOGICAL-MECHANISMS OF THE ANALGESIC EFFECT OF NEUROTENSIN [J].

BEHBEHANI, MM .

ANNALS OF THE NEW YORK ACADEMY OF SCIENCES-SERIES, 1992, 668 :253-265

[4] HYPOTHERMIA AND INTOLERANCE TO COLD INDUCED BY INTRACISTERNAL ADMINISTRATION OF HYPOTHALAMIC PEPTIDE NEUROTENSIN [J].

BISSETTE, G ;

NEMEROFF, CB ;

LOOSEN, PT ;

PRANGE, AJ ;

LIPTON, MA .

NATURE, 1976, 262 (5569) :607-609

[5] NEUROTENSIN-CONTAINING NEURONS IN THE CANINE ENTERIC INNERVATION [J].

BUCHAN, AMJ ;

BARBER, DL .

NEUROSCIENCE LETTERS, 1987, 76 (01) :13-17

[6]

Cochrane D E, 1990, Prog Med Chem, V27, P143, DOI 10.1016/S0079-6468(08)70291-1

[7] THE NONPEPTIDE NEUROTENSIN ANTAGONIST, SR-48692 USED AS A TOOL TO REVEAL PUTATIVE NEUROTENSIN RECEPTOR SUBTYPES [J].

DUBUC, I ;

COSTENTIN, J ;

TERRANOVA, JP ;

BARNOUIN, MC ;

SOUBRIE, P ;

LEFUR, G ;

ROSTENE, W ;

KITABGI, P .

BRITISH JOURNAL OF PHARMACOLOGY, 1994, 112 (02) :352-354

[8]

Ferris C.F., 1989, HDB PHYSL, P559

[9] EVIDENCE FOR NEUROTENSIN AS A NON-ADRENERGIC, NON-CHOLINERGIC NEUROTRANSMITTER IN GUINEA-PIG ILEUM [J].

GOEDERT, M ;

HUNTER, JC ;

NINKOVIC, M .

NATURE, 1984, 311 (5981) :59-62

[10] BIOCHEMICAL AND PHARMACOLOGICAL PROFILE OF A POTENT AND SELECTIVE NONPEPTIDE ANTAGONIST OF THE NEUROTENSIN RECEPTOR [J].

GULLY, D ;

CANTON, M ;

BOIGEGRAIN, R ;

JEANJEAN, F ;

MOLIMARD, JC ;

PONCELET, M ;

GUEUDET, C ;

HEAULME, M ;

LEYRIS, R ;

BROUARD, A ;

PELAPRAT, D ;

LABBEJULLIE, C ;

MAZELLA, J ;

SOUBRIE, P ;

MAFFRAND, JP ;

ROSTENE, W ;

KITABGI, P ;

LEFUR, G .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (01) :65-69

← 1 2 3 →