The actions of metabolic inhibition on human detrusor smooth muscle contractility from stable and unstable bladders

Abstract

Objectives To determine the important cellular site(s) of action of a brief exposure to NaCN (chosen to reduce mitochondrial respiration and hence mimic cellular hypoxia) on the mechanical properties and regulation of intracellular [Ca 2+ (15)% in the two groups; the reduction in the unstable was signi®cantly less than in the stable group. NaCN similarly reduced the response to 10 mmol/L caffeine, but had no effect on the KCl-induced contraction. NaCN signi®cantly increased the resting sarcoplasmic [Ca 2+ ] and attenuated the calcium transients evoked by carbachol and caffeine, but again had no effect on the KClinduced transient. The reduction of the carbachol calcium transient was also less in cells from unstable bladders than in those from stable bladders. There was no effect of NaCN on intracellular pH, except for a brief, transient alkalosis. Conclusions NaCN reduces both the contraction and Catransient to carbachol by reducing Ca 2+ accumulation by intracellular stores, because the carbachol-and caffeine-evoked responses were similar. Any effect on transmembrane Ca 2+¯u x was minimal because there was no effect on KCl-induced responses. The greater resilience of tissue from unstable bladders to acute cellular hypoxia may re¯ect some adaptation acquired in vivo.

Loss of ryanodine receptor calcium‐release channel expression associated with overactive urinary bladder smooth muscle contractions in a detrusor instability model

“…Moreover, caffeine increases intracellular levels of cAMP via its phosphodiesterase activity; cAMP causes muscle relaxation, and might directly influence the [Ca 2+ ] i ‐tension relationship. If so, the latter would play a major role [31,32].…”

Quantitative Proteomic Analysis Reveals Caffeine‐Perturbed Proteomic Profiles in Normal Bladder Epithelial Cells

“…A separate study using a mouse model found that oral caffeine administration resulted in detrusor overactivity and increased bladder sensory signaling . Further studies found similar effects on the detrusor muscle in humans . However, the direct effects of caffeine, its delivery into cells, and its mechanisms remain unestablished.…”

Caffeine Ingestion Causes Detrusor Overactivity and Afferent Nerve Excitation in Mice

“…In vitro caffeine appears to have an excitatory effect on the human detrusor smooth muscle. 7 A single study of the effects of caffeine ingestion on bladder contractility in diabetic rats showed that chronic oral administration of caffeine or coffee increased the contractility of isolated detrusor smooth muscle strips. 8 The group found an increased cyclic adenosine monophosphate concentration in the bladder of caffeine treated animals and postulated that this was the mechanism underlying the observed effect.…”