Somatostatin receptor subtypes 2 and 5 mediate inhibition of egg yolk-induced gall bladder emptying in mice.
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.
Kaczmarek
P
P
Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Interdisziplinäres Stoffwechsel-Centrum: Endokrinologie, Diabetes und Stoffwechsel, Charité - Universitätsmedizin 13353 Berlin, Germany.
Singh
V
V
Cashen
D E
DE
Yang
L
L
Berk
S
S
Pasternak
A
A
Xiong
Y
Y
Shen
D-M
DM
Hutchins
S M
SM
Chapman
K
K
Wiedenmann
B
B
Schaeffer
J M
JM
Strowski
M Z
MZ
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
D011506:Proteins; D017481:Receptors, Somatostatin; C035737:major urinary proteins; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D015282:Octreotide