Anticholinergic and calcium antagonistic activities of NS-21 contribute to the inhibition of rat urinary bladder contractions

Abstract 1. 1. Pharmacological characteristics of NS-21 and its main metabolite, RCC-36, in the inhibition of rat urinary bladder contractions were investigated both in vitro and in vivo 2. 2. NS-21 and RCC-36 inhibited muscarinic receptor bindings to rat bladder membranes with [ 3 H]3-quinuclidinyl bezilate (pKi 6.19 and 7.24, respectively), whereas they failed to inhibit the following receptor bindings: adrenergic (α 1 , α 2 and β), dopaminergic (D 1 and D 2 ), adenosine (A 1 and A 2 ), histaminergic (H 1 ) and opioid (μ, δ and κ) receptors. 3. 3. NS-21 and RCC-36 suppressed carbachol-induced contractions of isolated rat detrusor strips in competitive (pA 2 6.80 and 7.93, respectively) and noncompetitive (pD′ 2 5.93 and 5.77, respectively) manners. 4. 4. NS-21 and RCC-36 inhibited CaCl 2 -induced contractions of rat detrusor strips in the presence of 100 mM K + (pIC 50 6.54 and 5.76, respectively), as well as the 100 mM K + -induced 45 Ca influx into the isolated bladder strips at ≥1 μM 5. 5. Electrical stimulation of the peripheral end of the pelvic nerve in anesthetized rats induced bladder contractions composed of two phases: an initial phasic contraction that was weakly suppressed by atropine, and a tonic contraction that was strongly suppressed by atropine. NS-21 suppressed both contractions to the same degree (ID 50 2.65 and 2.19 mg/kg, IV, respectively). RCC-36 suppressed the tonic contraction (ID 50 1.20 mg/kg, IV) more markedly than the initial contraction (ID 50 7.43 mg/kg, IV) 6. 6. These results suggest that NS-21 and RCC-36 suppressed bladder contractions owing to their anticholinergic and calcium antagonistic activities.