Otenzepad shows two populations of binding sites in human gastric smooth muscle.

Abstract

Cholinergic agonists and antagonists frequently used for gastrointestinal motility disorders often produce adverse effects. A possible explanation for this is the presence of similar muscarinic receptor subtypes on smooth muscle from different gastrointestinal organs. The aim of this study was to characterize muscarinic receptor subtypes in human gastric smooth muscle with receptor binding methods. N-[3H]Methylscopolamine ([3H]NMS) saturation experiments showed a homogeneous population of noninteracting binding sites (KD = 0.76 +/- 0.07 nM, Bmax = 46.94 +/- 3.69 fmol/mg of tissue protein, nH = 0.99 +/- 0.01). The rank order of inhibition of [3H]NMS binding by nonlabelled compounds was atropine >> otenzepad >> pirenzepine. Atropine and pirenzepine bound to a homogeneous population of binding sites. The inhibition of [3H]NMS binding by otenzepad showed two populations of receptors (nH < 1, p < 0.01), whose apparent Ki1 of 298 +/- 40 nM and apparent Ki2 of 3.463 +/- 0.62 mM were similar to those reported for the M2 and M3 muscarinic receptor subtypes. The M2 subtype was the more abundant of the two, representing 79.12 +/- 5.48% of the total population. We conclude that two muscarinic receptor subpopulations similar to the M2 and M3 subtypes are present in human gastric smooth muscle and that the M2-like receptor is the more abundant of the two.