OTENZEPAD SHOWS 2 POPULATIONS OF BINDING-SITES IN HUMAN GASTRIC SMOOTH-MUSCLE

Cholinergic agonists and antagonists frequently used for gastrointesti nal motility disorders often produce adverse effects. A possible expla nation for this is the presence of similar muscarinic receptor subtype s on smooth muscle from different gastrointestinal organs. The aim of this study was to characterize muscarinic receptor subtypes in human g astric smooth muscle with receptor binding methods. N-[H-3]Methylscopo lamine (r[H-3]NMS) saturation experiments showed a homogeneous populat ion of noninteracting binding sites (K-D = 0.76 +/- 0.07 nM, B-max = 4 6.94 +/- 3.69 fmol/mg of tissue protein, n(H) = 0.99 +/- 0.01). The ra nk order of inhibition of [H-3]NMS binding by nonlabelled compounds wa s atropine much greater than otenzepad much greater than pirenzepine. Atropine and pirenzepine bound to a homogeneous population of binding sites. The inhibition of [H-3]NMS binding by otenzepad showed two popu lations of receptors (n(H) < 1, p < 0.01), whose apparent K-i1 of 298 +/- 40 nM and apparent K-i2 of 3.463 +/- 0.62 mM were similar to those reported for the M(2) and M(3) muscarinic receptor subtypes. The M(2) subtype was the more abundant of the two, representing 79.12 +/- 5.48 % of the total population. We conclude that two muscarinic receptor su bpopulations similar to the M(2) and M(3) subtypes are present in huma n gastric smooth muscle and that the M(2)-like receptor is the more ab undant of the two.