title: Somatostatin receptor subtypes 2 and 5 mediate inhibition of egg yolk-induced gall bladder emptying in mice.
abstract: BACKGROUND
  Somatostatin inhibits gall bladder contraction. Impaired gall bladder emptying is associated with gall bladder stone formation. The incidence of cholecystolithiasis is high in patients treated with a somatostatin agonist octreotide, which predominantly interacts with somatostatin receptor subtype 2 (SSTR2). Therefore, it is believed that SSTR2 regulates gall bladder contraction; however, evidence has not been provided. Here, we evaluate the effects of SSTR1-SSTR5-selective agonists on egg yolk-induced gall bladder contraction in mice.
  
  
  METHODS
  Homozygous deletion of SSTR2 and SSTR5 was generated by cross-mating of SSTR2(-/-) with SSTR5(-/-) mice. Mice of different genotypes were injected with SSTR1-5-selective agonists or octreotide 15 min before induction of gall bladder emptying by egg yolk. One hour later, gall bladders were removed and weighed.
  
  
  RESULTS
  Egg yolk-reduced gall bladder weights in all mice, irrespective of their genotype. Octreotide was the most potent inhibitor of gall bladder emptying in wild-type mice. In contrast, agonists with high selectivity for SSTR2 or SSTR5 inhibited gall bladder emptying by approximately 50-60%, whereas SSTR1-, SSTR3- and SSTR4-selective agonists failed to influence gall bladder contraction. In SSTR2(-/-) mice, octreotide and an SSTR5-selective agonist inhibited gall bladder emptying by approximately 50%, whereas SSTR2-selective agonists were inactive. Octreotide inhibited gall bladder emptying in SSTR5(-/-) mice by approximately 50%, without any effect in SSTR2(-/-)/SSTR5(-/-) mice.
  
  
  CONCLUSIONS
  Our study provides evidence for the role of SSTR2 and SSTR5 in regulating gall bladder emptying in mice.
authors.affiliation: Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Interdisziplinäres Stoffwechsel-Centrum: Endokrinologie, Diabetes und Stoffwechsel, Charité - Universitätsmedizin 13353 Berlin, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Kaczmarek
authors.forename: V
authors.initials: V
authors.lastname: Singh
authors.forename: D E
authors.initials: DE
authors.lastname: Cashen
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.forename: S
authors.initials: S
authors.lastname: Berk
authors.forename: A
authors.initials: A
authors.lastname: Pasternak
authors.forename: Y
authors.initials: Y
authors.lastname: Xiong
authors.forename: D-M
authors.initials: DM
authors.lastname: Shen
authors.forename: S M
authors.initials: SM
authors.lastname: Hutchins
authors.forename: K
authors.initials: K
authors.lastname: Chapman
authors.forename: B
authors.initials: B
authors.lastname: Wiedenmann
authors.forename: J M
authors.initials: JM
authors.lastname: Schaeffer
authors.forename: M Z
authors.initials: MZ
authors.lastname: Strowski
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000235:genetics; D004530:Egg Yolk; D005704:Gallbladder / Q000187:drug effects / Q000378:metabolism*; D016473:Gallbladder Emptying / Q000187:drug effects / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D015282:Octreotide / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D011507:Proteinuria / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism
chemical_list: D011506:Proteins; D017481:Receptors, Somatostatin; C035737:major urinary proteins; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D015282:Octreotide