PURPOSE: Recent studies using vascular and gut smooth muscles indicate that contractile receptor agonists may activate post-receptor down-regulatory mechanisms causing a temporary reduction in the strength of subsequent @entity2472 . Our data indicate a similar mechanism exists in detrusor smooth muscle of the urinary bladder. MATERIALS AND METHODS: Each isolated strip of female @entity95 detrusor was placed in a tissue bath, secured to an isometric force transducer, and length-adjusted until depolarization with 110 mM @entity4338 produced a maximum contraction (S0). Subsequent @entity2472 were normalized to S0 (S/S0) or to a first stimulus with 30 mM @entity4338 or @entity5834 (S/S1). Tissues were pretreated with the muscarinic receptor agonist, @entity10257 (BE), then stimulated with @entity4338 , @entity5834 , or @entity9898 to identify potential post-receptor down-regulation. RESULTS: Contractions induced by 30 mM @entity4338 had three phases labeled fast peak (FP), slow peak (SP) and steady-state (SS). In tissues exposed for 30 min. to a maximum BE concentration then washed for 5 min., the @entity4338 -induced FP and SP, but not SS, responses were reduced by approximately 40%. Smaller reductions in peak @entity4338 -induced @entity2472 occurred in tissues pretreated for a shorter duration or with a 100-fold lower BE concentration. This down-regulation induced by @entity10257 pretreatment was reversible, lasting approximately 1-2 h. Not only were @entity4338 -induced @entity2472 reduced by BE pretreatment, but also those produced by the intracellular @entity141 -mobilizer, @entity5834 , and the L-type @entity141 channel agonist, @entity9898 . CONCLUSIONS: Pretreatment of isolated strips of @entity95 detrusor with a muscarinic receptor agonist produced short-term down-regulation of @entity4338 -induced peak @entity2472 that may have involved inhibition of both influx of extracellular @entity141 and release of intracellular @entity141 . Reductions in the degree of this novel modulatory response during disease conditions and aging could enhance contractile activity, possibly causing detrusor instability.

XXXX activates a post-receptor negative feedback mechanism in @entity95 urinary bladder smooth muscle.

@entity4338 :: ('CHEBI:32588', 'Chemical') :: ['KCl'] @entity95 :: ('9986', 'Species') :: ['rabbit'] @entity5834 :: ('MESH:D002110', 'Chemical') :: ['caffeine'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca2+', 'Ca(2+)'] @entity9898 :: ('MESH:D001498', 'Chemical') :: ['Bay k 8644'] @entity10257 :: ('MESH:D018723', 'Chemical') :: ['bethanechol'] @entity2472 :: ('MESH:C536214', 'Disease') :: ['contractions']
@entity10257 :: (MESH:D018723,Chemical) :: ['Bethanechol']
