Effect of somatostatin and thyrotropin-releasing hormone on cholecystokinin-induced gallbladder emptying

Abstract

The effect of somatostatin (0.05 and 1.5 micrograms/kg/hr) and of thyrotropin-releasing hormone (0.1 and 1.0 microgram/kg/hr) on cholecystokinin-induced gallbladder emptying was studied in healthy volunteers by means of real-time ultrasonography. In addition, the action of increasing doses (0.05, 0.15, 0.45, and 1.35 micrograms/kg/hr) of somatostatin on resting gallbladder volume was also evaluated. Somatostatin, at the dose of 0.05 microgram/kg/hr (shown to produce blood levels similar to those measured after a meal) significantly inhibited the gallbladder contraction in response to cholecystokinin. Kinetic analysis showed that the interaction of somatostatin and cholecystokinin is of the noncompetitive type. The higher dose of the peptide (1.5 microgram/kg/hr) completely suppressed cholecystokinin-induced gallbladder contraction. In experiments carried out using somatostatin alone, a progressive increase in gallbladder volume in response to increasing doses of peptide was observed. The administration of either dose of thyrotropin-releasing hormone did not affect gallbladder emptying in any of the subjects studied. It is concluded that somatostatin is a potent inhibitor of cholecystokinin action on the gallbladder. The clear effectiveness of a very low, presumably physiological, dose indicates that somatostatin may play a physiological role in the regulation of gallbladder motor activity and provides further evidence that the peptide may act as a true hormone in man. Thyrotropin-releasing hormone does not seem to affect gallbladder motility, at least under the experimental conditions of the present study.

Effects of somatostatin and loxiglumide on gallbladder motility

“…Previous experiments have examined the inhibitory effect of somatostatin on gallbladder contraction due either to administration of CCK or bethanechol, or to meal ingestion or sham feeding. Gullo et al found that somatostatin non-competively inhibited the effects of CCK infusion on gallbladder contraction and suggested that somatostatin acted on a different receptor in gallbladder muscle with a contrary effect to that of CCK [5]. Fischer et al demonstrated that somatostatin was able completely to abolish the gallbladder emptying response to liquid and solid meals, and to cholinergic stimulation by bethanechol and sham feeding.…”

“…The risk of gallstones is also increased in acromegalics on long term treatment with the somatostatin analogue octreotide (SMS 201-995) [3,4]. The mechanism of this effect is not known, but inhibition of gallbladder contraction by somatostatin is generally believed like the crucial mechanism [2,5]. Biliary stasis may provide the time required for the precipitation of cholesterol microcrystals from bile supersaturated with cholesterol.…”

“…It has been shown to inhibit gallbladder contraction in response to infusion of exogenous cholecystokinin (CCK) [2,5] and meal stimuli [2]. Somatostatin also exerts an inhibitory effect on cholecystokinin release from the upper small intestinal mucosa [6][7][8], and on acetylcholine release from the gallbladder myenteric plexus upon which cholecystokinin is partly dependent for its action [9].…”

Study of the Effect of Neurotensin on Meal- and Cerulein-lnduced Gallbladder Contraction

“…We used three dimensions: length (longitu dinal diameter), width (side-to-side diameter) and height (anteroposterior diameter) to calculate the vol ume on the assumption that the shape of the gallblad der approximated a solid whose sections are elliptic with the eccentricity depending on the eccentricity at the level of the maximal transverse section. The method has been described in detail in previous papers [12,13], Each subject underwent 2 tests, in random order, on 2 separate days, in the morning after an overnight fast. On one day, 6 of the 11 subjects ingested a fatty liquid meal (Colecisto test: lntermedi Medicinali Sintetici.…”

Gallstones during Octreotide Therapy

“…It was not suprising, therefore, that several groups of investigators showed that native somatostatin also inhibited GB contraction in response to food or to other cholecystokinetic stimuli [16,[39][40][41][42][43], However, in the context of GBS pathogenesis, somatostatin has other potentially important effects on the biliary system includ ing a reduction in hepatic bile How in both animals [44][45][46] and man [47,48].…”