The basis for progesterone impairment of gallbladder contractility in male guinea pigs in vitro

Bob Kiaii, Qi Wei Xu, Eldon A. Shaffer

Research output: Contribution to journalArticlepeer-review

Abstract

Progesterone suppresses gallbladder smooth muscle function but its exact mechanism is unknown. We sought to determine the cellular site where progesterone impairs gallbladder smooth muscle. Sixty-four adult male guinea pigs were injected with either progesterone (2 mg/kg/day sc) or normal saline (controls) for 7 days. Dose-response curves of gallbladder strips to cholecystokinin (CCK), bethanechol, and potassium (K+) were constructed in vitro. To better define the basis for the progesterone effect, gallbladder contractile response was determined to specific agonists: aluminum fluoride and mastoparan (direct G-protein activators), cyclopiazonic acid (CPA), and a calcium ionophore (A-23187). Gallbladder from animals on progesterone exhibited a marked decrease in contractile response to CCK and bethanechol compared with controls (P < 0.05). Further, gallbladder contraction remained depressed (P < 0.05) in progesterone-treated animals, when the G protein was directly activated with aluminum fluoride and mastoparan. In contrast, the responses to K+ (acting independent of receptor G-protein) and to A-23187 and CPA (agonists that bypassed the membrane) were comparable in both groups (NS). It is concluded that progesterone directly inhibits gallbladder smooth muscle contractility in vitro to a standard hormone, CCK, and a cholinergic agent. Such depressed contraction is not due to an altered contractile machinery, since it is normal with agonists that act independently of G- protein activation. Progesterone thus interferes with signaling through the G-protein, either by directly becoming closely associated with the cell membrane or by indirectly perturbing its receptor products.

Original languageEnglish (US)
Pages (from-to)97-102
Number of pages6
JournalJournal of Surgical Research
Volume79
Issue number2
DOIs
StatePublished - Oct 1998
Externally publishedYes

Keywords

  • Cholesterol gallstone disease
  • Gallbladder contractility
  • Guinea pig
  • Progesterone

ASJC Scopus subject areas

  • Surgery

Fingerprint Dive into the research topics of 'The basis for progesterone impairment of gallbladder contractility in male guinea pigs in vitro'. Together they form a unique fingerprint.

Cite this