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 μmol/liter) increased the prostaglandin stimulated short-circuit current by 12.3 ± 1 and 11.0 ± 1 μA/cm2, respectively. Similarly, analogs selective for somatostatin receptor subtypes 2 and 5 (1 μmol/liter) produced an increase of short-circuit current of 11.7 ± 1 and 13.2 ± 1 μA/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 μA/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.
Similar content being viewed by others
REFERENCES
Yamada T, Chiba T: Somatostatin. In Handbook of Physiology, Section 6, The Gastrointestinal System, Neural and Endocrine Control, Volume II. G Makhlouf (ed). Bethesda, Maryland, American Physiological Society, 1989, pp 431–454
Dharmasathaphorn K, Sherwin RS, Dobbins JW: Somatostatin inhibits fluid secretion in the rat jejunum. Gastroenterology 78:813–820, 1980
Knobloch SF, Diener M, Rummel W: Antisecretory effects of somatostatin and vasopressin in the rat colon descendens in vitro. Regul Pept 25:75–85, 1989
Warhurst G, Turnberg LA, Higgs NB, Tonge A, Grundy J, Fogg KE: Multiple G-protein dependent pathways mediate the antisecretory effects of somatostatin and clonidine in the HT29-19A colonic cell line. J Clin Invest 92:603–611, 1993
Warhurst G, Barbezat GO, Higgs NB, Reyl-Desmars F, Lewin MJM, Coy DH, Ross I, Grigor MR: Expression of somatostatin receptor genes and their role in inhibiting Cl- secretion in HT-29cl.19A colonocytes. Am J Physiol 269:G729–G736, 1995
Patel YC, Greenwood M, Panetta R, Hukovic N, Grigorakis S, Robertson L-A, Srikant CB: Molecular biology of somatostatin receptor subtypes. Metabolism 45:31–38, 1996
Coy DH, Taylor JE: Receptor-specific somatostatin analogs: Correlations with biological activity. Metabolism 45:21–23, 1996
Arn M, Butt AG, Lubcke R, Ross I, Grigor M, Warhurst G, Barbezat GO: Somatostatin and octreotide stimulate short circuit current in the human colonic epithelium. Dig Dis Sci 45:2100–2107, 2000
Warhurst G, Higgs NB, Fakhoury H, Warhurst AC, Garde J, Coy DH: Somatostatin receptor subtype 2 mediates somatostatin inhibition of ion secretion in rat distal colon. Gastroenterology 111:325–333, 1996
Chomczynski P, Sacchi N: Single step method of RNA isolation by guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159, 1987
Rossowski WJ, Coy DH: Potent inhibitory effects of a type four receptor-selective somatostatin analog on rat insulin release. Biochim Biophys Res Commun 197:366–371, 1993
Laws SAM, Gough AC, Evans AA, Bains MA, Primrose JN: Somatostatin receptor subtype mRNA expression in human colorectal cancer and normal colonic mucosae. Br J Cancer 75:360–366, 1997
Warhurst G, Higgs NB, Grigor MR, Ross I, Barbezat GO: Expression of multiple somatostatin receptor genes in human colonic epithelial cells. Biochem Soc Trans 23:18s, 1995
Reisine T, Kong H, Raynor K, Yano H, Takeda J, Yasuda K, Bell GI: Splice variant of the somatostatin receptor 2 subtype, somatostatin receptor 2B, couples to adenylyl cyclase. Mol Pharmacol 44:1016–1020, 1993
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hope, N., Butt, G., Ross, I. et al. Somatostatin Enhances cAMP-Dependant Short-Circuit Current in Human Colon via Somatostatin Receptor Subtype-2. Dig Dis Sci 46, 2499–2503 (2001). https://doi.org/10.1023/A:1012392307462
Issue Date:
DOI: https://doi.org/10.1023/A:1012392307462