title: Somatostatin receptor subtype 2 mediates somatostatin inhibition of ion secretion in rat distal colon.
abstract: OBJECTIVE
  Somatostatin peptides are potent inhibitors of intestinal ion secretion, providing the rationale for their use in treating secretory diarrhea. However, the nature of the receptors that mediate these effects is unclear. The aims of this study were to investigate expression of somatostatin receptor subtypes (SSTRs) 1-5 in rat colonic epithelium and to identify which subtype(s) mediate inhibition of adenosine 3', 5'-cyclic monophosphate (cAMP)-activated secretion using SSTR-selective analogues.
  
  
  METHODS
  SSTR expression was determined by reverse-transcription polymerase chain reaction and immunoblotting. Effects of somatostatin analogues on electrogenic ion secretion were studied in isolated colonic mucosa mounted in Ussing chambers.
  
  
  RESULTS
  Crypt epithelium expressed messenger RNA for SSTR1 and SSTR2 and low levels of SSTR5. A splice variant of SSTR2 (SSTR2B) was also detected. The SSTR2 selective analogue NC-812 was a potent inhibitor of forskolin-activated secretion and cAMP accumulation. In contrast, peptides selective for SSTR3 (DC-25/12) and SSTR5 (DC-23/99) were weak inhibitors of secretion. NC-812 also inhibited dibutyryl cAMP-activated secretion, indicating a site of action distal to cAMP production. Immunoblot analysis confirmed expression of a 93-kilodalton SSTR2 protein in crypt cell membranes.
  
  
  CONCLUSIONS
  SSTR2 receptors expressed by colonocytes mediate somatostatin's antisecretory actions in rat colon. Somatostatin analogues directed to specific SSTRs may provide the basis for more selective antidiarrheal drugs.
authors.affiliation: Department of Medicine, University of Manchester, Hope Hospital, Salford, England.
authors.forename: G
authors.initials: G
authors.lastname: Warhurst
authors.forename: N B
authors.initials: NB
authors.lastname: Higgs
authors.forename: H
authors.initials: H
authors.lastname: Fakhoury
authors.forename: A C
authors.initials: AC
authors.lastname: Warhurst
authors.forename: J
authors.initials: J
authors.lastname: Garde
authors.forename: D H
authors.initials: DH
authors.lastname: Coy
mesh_terms: D000818:Animals; D001483:Base Sequence; D003106:Colon / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004573:Electrolytes / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D015151:Immunoblotting; D007477:Ions; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000502:physiology*; D013004:Somatostatin / Q000502:physiology*
chemical_list: D004573:Electrolytes; D007477:Ions; D017481:Receptors, Somatostatin; D013004:Somatostatin; C093733:somatostatin receptor 2; D000242:Cyclic AMP