Effects of Calcium, Calcium Channel Blockers and Bay K 8644 on Contractions Induced by Muscarinic Receptor Stimulation of Isolated Bladder Muscle from Rabbit and Man

Abstract

In isolated bladder smooth muscle from both rabbit and man, carbachol-induced contractions were reduced by the calcium channel blocker nifedipine, whereas the calcium channel promotor Bay K 8644 had no effect. In nominally calcium-free medium containing 10(-4) M EGTA, carbachol-induced contractions were reduced by 69% (rabbit) and 87% (man). These contractions were abolished by nifedipine, whereas Bay K 8644 significantly increased their amplitude, in rabbit preparations almost to control level. Electrical field stimulation produced contractions which could be suppressed by scopolamine by about 50% (rabbit) and more than 90% (man). These contractions were abolished by calcium-free medium (10(-4) M EGTA), suppressed by nifedipine, but significantly enhanced by Bay K 8644. The depressant effects of nifedipine, verapamil and diltiazem were reversed by Bay K 8644. The calcium channel blockers relaxed K+-induced contractions to base line, and this action was counteracted by Bay K 8644, less effectively when relaxations were induced by diltiazem. It is concluded that contractions produced by muscarinic receptor stimulation are primarily dependent on calcium bound to the outside of the membrane of the smooth muscle, and/or coming from the extracellular medium. Electrically evoked, scopolamine sensitive contractions seem to be mediated by a mechanism different from that of contractions produced by exogenously added muscarinic receptor agonist. The present data support the view that combined blockade of muscarinic receptors and calcium channels is an effective way of inhibiting bladder contractions in both rabbit and man.

Multiple sources of calcium for contraction of the human urinary bladder muscle

“…Fovaeus et al, 1987). This could occur through activation of receptor-operated mechanisms as proposed for many other smooth muscles (Somlyo & Somlyo, 1968;Bolton, 1979).…”

“…In vivo studies in anaesthetized rats suggested that Ca mobilization via nifedipineresistant pathways might be a relevant mode of contraction during a physiological-like event, that is, volume-evoked bladder voiding (micturition reflex) (Maggi et al, 1988a). Fovaeus et al (1987) investigated the effect of nifedipine and Bay K 8644 on carbachol-induced contractions of human isolated bladder muscle and concluded that both voltagedependent and receptor-operated Ca channels mediate this response. Recently we studied the effect of endothelin, an endothelium-derived vasconstrictor peptide proposed to act as an endogenous agonist at dihydropyridine-sensitive Ca channels in the human isolated bladder (Maggi et al, 1989a) and found that the contractile response to this peptide was almost totally nifedipine-resistant while the KCI-induced contraction was abolished by nifedipine-pretreatment. These observations prompted us to re-address N02/02 (1/2) and halothane (0.6-1 %).…”

Pharmacology of the Lower Urinary Tract: Basis for Current and Future Treatments of Urinary Incontinence

“…Previous studies have indicated an important role for extracellular calcium in muscarinic receptor activation of the human bladder (Fovaeus et al, 1987), but the sources of calcium used for contractile activation have been a matter of debate (Andersson 1993). As pointed out by Hashitani et al (2000), in most studies of the contribution of IP 3 production to muscarinic receptormediated contractions in the detrusor, relatively high concentrations of muscarinic receptor agonists have been used.…”

Effect of Magnesium on the Contraction of Whole Rabbit Bladder in vitro

“…The effect of magnesium in the presence of calcium chan nel ligands supports the hypothesis that magnesium in hibits calcium transport via the calcium channels [14], Verapamil and BAY-K8644 both work on voltagedependent calcium channels. Calcium channel blockers including verapamil inhibit the calcium influx through calcium channels on the smooth muscle cell membrane, which results in decrease in the detrusor contraction induced by both intramural nerve stimulation and direct cholinergic receptor stimulation [21,22], However, BAY-K8644, which is believed to prolong the opening time of…”