Guinea pig 5-HT transporter: cloning, expression, distribution, and function in intestinal sensory reception

被引：166

作者：

Chen, JX ^{[1
]}

Pan, H ^{[1
]}

Rothman, TP ^{[1
]}

Wade, PR ^{[1
]}

Gershon, MD ^{[1
]}

机构：

[1] Columbia Univ Coll Phys & Surg, Dept Anat & Cell Biol, New York, NY 10032 USA

来源：

AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 1998年 / 275卷 / 03期

关键词：

serotonin; serotonin-selective reuptake inhibitors; fluoxetine; enteric nervous system; peristaltic reflex; enterochromaffin cells;

D O I：

10.1152/ajpgi.1998.275.3.G433

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Studies of the guinea pig small intestine have suggested that serotonin (5-HT) may be a mucosal transmitter that stimulates sensory nerves and initiates peristaltic and secretory reflexes. We tested the hypothesis that guinea pig villus epithelial cells are able to inactivate 5-HT because they express the same 5-HT transporter as serotonergic neurons. A full-length cDNA, encoding a 630-amino acid protein (89.2% and 90% identical, respectively, to the rat and human 5-HT transporters) was cloned from the guinea pig intestinal mucosa. Evidence demonstrating that this cDNA encodes the guinea pig 5-HT transporter included 1) hybridization with a single species of mRNA (similar to 3.7 kb) in Northern blots of the guinea pig brain stem and mucosa and 2) uptake of [H-3]5-HT by transfected HeLa cells via a saturable, high-affinity (Michaelis constant 618 nM, maximum velocity 2.4 x 10(-17) mol.cell(-1).min(-1)), Na+-dependent mechanism that was inhibited by chlorimipramine > imipramine > fluoxetine > desipramine > zimelidine. Expression of the 5-HT transporter in guinea pig raphe and enteric neurons and the epithelium of the entire crypt-villus axis was demonstrated by in situ hybridization and immunocytochemistry. Inhibition of mucosal 5-HT uptake potentiates responses of submucosal neurons to mucosal stimulation. The epithelial reuptake of 5-HT thus appears to be responsible for terminating mucosal actions of 5-HT.

引用

页码：G433 / G448

页数：16

共 51 条

[1]

Barker EL, 1996, MOL PHARMACOL, V50, P957

[2]

BARKER EL, 1994, MOL PHARMACOL, V46, P799

[3] EFFECTS OF 5-HYDROXYTRYPTAMINE ON DISCHARGE OF VAGAL MUCOSAL AFFERENT-FIBERS FROM THE UPPER GASTROINTESTINAL-TRACT OF THE FERRET [J].

BLACKSHAW, LA ;

GRUNDY, D .

JOURNAL OF THE AUTONOMIC NERVOUS SYSTEM, 1993, 45 (01) :41-50

[4] CLONING AND EXPRESSION OF A FUNCTIONAL SEROTONIN TRANSPORTER FROM RAT-BRAIN [J].

BLAKELY, RD ;

BERSON, HE ;

FREMEAU, RT ;

CARON, MG ;

PEEK, MM ;

PRINCE, HK ;

BRADLEY, CC .

NATURE, 1991, 354 (6348) :66-70

[5]

BLAKELY RD, 1993, MOL BIOL FUNCTION CA, P284

[6]

BLASCHKO H, 1966, HDB EXPT PHARM, P212

[7]

BULBRING E, 1958, BRIT J PHARM CHEMOTH, V13, P444

[8]

BULBRING E, 1959, J PHYSIOL-LONDON, V146, P29

[9]

BULBRING E, 1959, J PHYSIOL-LONDON, V146, P18

[10]

BULBRING E, 1958, J PHYSIOL-LONDON, V140, P381

← 1 2 3 4 5 6 →