Somatostatin enhances cAMP-dependent short-circuit current in human colon via somatostatin receptor subtype-2.

Abstract:

:Somatostatin inhibits colonic ion secretion in animal models and cultured intestinal cell lines via somatostatin receptor subtype 2 and subtype 1, respectively. In a recent in vitro ion transport study of the human colon, somatostatin was shown to stimulate short-circuit current, a measure of electrogenic ion transport. In this study we have used the reverse-transcription polymerase chain reaction (RT-PCR) and measurements of changes in short-circuit current (Isc) in response to receptor subtype-specific analogs of somatostatin, to define the somatostatin receptor subtype responsible for the stimulation of short-circuit current in human colon. Somatostatin receptor subtypes 1, 2, and 5, but not 3 and 4, were detected in the human colonic epithelium. Measurements of short-circuit current showed somatostatin and octreotide (1 micromol/liter) increased the prostaglandin stimulated short-circuit current by 12.3+/-1 and 11.0+/-1 microA/cm2, respectively. Similarly, analogs selective for somatostatin receptor subtypes 2 and 5 (1 micromol/liter) produced an increase of short-circuit current of 11.7+/-1 and 13.2+/-1 microA/cm2, respectively. However, at a concentration (10 nmol/liter) near the EC50, the somatostatin receptor subtype 2 analog increased short-circuit current by 9+/-1 microA/cm2, whereas the receptor subtype 5 analog had no effect. There was no difference in receptor expression or effect of the peptides related to the anatomical site of tissue collection. In conclusion, human colonic mucosa expresses multiple somatostatin receptor subtypes, of which subtype 2 mediates the stimulatory effect of somatostatin on ion transport.

journal_name

Dig Dis Sci

authors

Hope N,Butt G,Ross I,Warhurst G,Arn M,Grigor M,Lubcke R,Barbezat GO

doi

10.1023/a:1012392307462

subject

Has Abstract

pub_date

2001-11-01 00:00:00

pages

2499-503

issue

11

eissn

0163-2116

issn

1573-2568

journal_volume

46

pub_type

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