Ligand Binding to Muscarinic Receptors in Intact Longitudinal Muscle Strips From Guinea‐pig Intestine

Abstract

The binding of ligands to muscarinic receptors in intact longitudinal muscle strips from guinea‐pig small intestine has been determined by measuring the inhibition of the irreversible binding of [3H]‐propylbenzilylcholine mustard ([3H]‐PrBCM). The IC50 values for inhibition of [3H]‐PrBCM binding by a given ligand were generally higher in intact strips than those reported for broken‐cell preparations. This effect is probably due, at least in part, to the presence of an access‐limitation factor in the kinetics of the irreversible binding of [3H]‐PrBCM to the intact tissue. The mean Hill coefficients for antagonist binding approached unity, but those for strong agonists were significantly less than unity. There was, with the possible exceptions of hexyltrimethylammonium and oxotremorine, reasonably good agreement with the Hill coefficients reported for brain homogenates.

The effect of gallamine, gallopamil and nifedipine on responses to acetylcholine and carbachol in the taenia of the guinea‐pig caecum

“…Evidence from binding studies in ileal tissue of multiple binding sites for muscarinic agonists (Ward & Young, 1977) and of different sources of calcium being available for contractions by cholinomimetics (Brading & Sneddon, 1980) led to the use of the 'calcium entry blockers'. If the two agonists were acting on the same receptor but on different binding sites, then there may be differences in the coupling of their receptor activation to contraction.…”

The Interaction of Amine Local Anaesthetics With Muscarinic Receptors

“…One point which may be noted is that none of the amines give Hill coefficients significantly < 1 and thus show no evidence of any selectivity between the two states of the muscarinic receptor which are apparently distinguished by the binding of muscarinic agonists (Birdsall & Hulme, 1976;Ward & Young, 1977;Birdsall et al, 1978).…”

“…muscarinic agonists, which in general appear to distinguish at least two independent binding sites (Birdsall & Hulme, 1976;, might be affected in a more complex manner by prilocaine, in analogy with its effects on the nicotinic acetylcholine receptor (Cohen et al, 1974;Heidmann & Changeux, 1978 (Ward & Young, 1977). The percentages of the high and low affinity sites were 25 + 3 and 67 + 3, respectively.…”

THE BINDING CHARACTERISTICS OF [3H]‐DIHYDROERGOCRYPTINE ON INTACT HUMAN PLATELETS

“…The majority of receptor studies have therefore been performed on subcellular tissue preparations, either in the form of a crude homogenate or as a purified receptor fraction. Comparisons between receptor binding characteristics in intact tissue and in homogenates are few but have revealed some significant differences between the two tissue preparations (Ward & Young, 1977;Gilbert, Hanley & Iversen, 1979). Platelets, being unicellular, are particularly useful cells in which to make such a comparison since the diffusional problem is 0007-1188/82/050121-10 $01.00 minimized.…”

“…In several of those cases investigated, a diffusion element appears to affect significantly the establishment of equilibrium (Ward & Young, 1977; Elliott, Tayler & Young, 1978) and attempts have been made to quantify this 'biophase' barrier (Rang, 1966;Thron & Waud, 1968). The majority of receptor studies have therefore been performed on subcellular tissue preparations, either in the form of a crude homogenate or as a purified receptor fraction.…”