NOVEL 5-HT2-LIKE RECEPTOR MEDIATES NEUROGENIC RELAXATION OF THE GUINEA-PIG PROXIMAL COLON

被引：15

作者：

BRIEJER, MR

AKKERMANS, LMA

LEFEBVRE, RA

SCHUURKES, JAJ

机构：

[1] JANSSEN RES FDN, DEPT GASTROINTESTINAL PHARMACOL, TURNHOUTSEWEG 30, B-2340 BEERSE, BELGIUM

[2] AGR UNIV WAGENINGEN, DEPT HUMAN & ANIM PHYSIOL, WAGENINGEN, NETHERLANDS

[3] STATE UNIV GHENT, SCH MED, HEYMANS INST PHARMACOL, B-9000 GHENT, BELGIUM

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 1995年 / 279卷 / 2-3期

关键词：

5-HT RECEPTOR; COLON; GUINEA PIG; GASTROINTESTINAL MOTILITY; ENTERIC NERVE; RELAXATION;

D O I：

10.1016/0014-2999(95)00146-C

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The aim of the current investigation was to characterize the 5-HT receptors that mediate neurogenic relaxation of the guinea-pig proximal colon. After blockade of 5-HT2A, 5-HT3 and 5-HT4 receptor-mediated contractions, 5-hydroxytryptamine (5-HT) induced relaxations yielding a biphasic concentration-response curve. Other tryptamines were also agonists with the following rank order of potency: 5-HT > 5-carboxamidotryptamine = 5-methoxytryptamine greater than or equal to alpha-methyl-5-HT (partial agonist) > tryptamine (partial agonist). 5-Hydroxytryptophan, 2-methyl-5-HT and N-methyltryptamine were virtually inactive as agonists. The curve to 5-HT was not affected by pargyline, citalopram, phentolamine, or by the 5-HT4 receptor antagonists 2-methoxy-4-amino-5-chloro-benzoic acid 2-(diethylamino)ethyl ester (SDZ 205-557) and (1-butyl-4-piperidinylmethyl)-8-amino-7- chloro-1,4-benzodioxan-5-carboxylate (SE 204070). 8-Hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), 5-methoxy-3[1,2,3,6-tetrahydroxypyridin-4-yl]-1H-indole (RU 24969), 2-(2,6-dimethoxyphenoxyethyl)aminomethyl- 1,4-benzodioxane (WE 4101), 1-(3-chlorophenyl)piperazine (mCPP), 1-(m-trifluoromethylphenyl)-piperazine (TFMPP), flesinoxan, sumatriptan and 6-chloro-2-(piperazinyl)-pyrazine (MK212) were inactive as 5-HT receptor agonists. The first phase of the curve to 5-HT was inhibited by: metergoline (pA(2) = 8.8 +/- 0.3, against 5-methoxytryptamine 9.3 +/- 0.3), methysergide (non-surmountable), methiothepin (nonsurmountable), spiroxatrine (non-surmountable), MK212 (non-surmountable), mesulergine (7.8 +/- 0.3), mCPP (7.1 +/- 0.1), mianserin (7.0 + 0.4), ritanserin (8.9 +/- 0.2), rauwolscine (7.0 +/- 0.2), yohimbine (6.2 +/- 0.2), 1-(1-naphthyl)-piperazine (7.7 +/- 0.2) and RU 24969 (6.4 +/- 0.1), but not by 1-(2-methoxyphenyl)-4-[4-(2-phthalimidobtyl]-piperazine (NAN-190), spiperone, sumatriptan, 8-OH-DPAT and flesinoxan. It is suggested that the 5-HT receptor under study could be considered an unknown 5-HT2-like receptor.

引用

页码：123 / 133

页数：11

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