A Comparison of Affinity Constants for Muscarine‐sensitive Acetylcholine Receptors in Guinea‐pig Atrial Pacemaker Cells at 29°c and in Ileum at 29°c and 37°c

Abstract

1 The affinity of 17 compounds for muscarine-sensitive acetylcholine receptors in atrial pacemaker cells and ileum of the guinea-pig has been measured at 290C in Ringer-Locke solution. Measurements were also made at 370C with 7 of them. 2 Some of the compounds had much higher affinity for the receptors in the ileum than for those in the atria. For the most selective compound, 4-diphenylacetoxy-N-methylpiperidine methiodide, the difference was approximately 20-fold. The receptors in the atria are therefore different in structure from those in the ileum. 3 The effects of temperature on affinity are not the same for all the compounds tested, indicating different enthalpies and entropies of adsorption and accounting for some of the difficulty experienced in predicting the affinity of new compounds.

Novel pharmacological profile of muscarinic receptors mediating contraction of the guinea-pig uterus

“…The affinities obtained at uterine muscarinic receptors of immature guinea-pigs were compared to those determined at M 1 (rabbit vas deferens), M 2 (guinea-pig atria) and M 3 receptors (guinea-pig ileum). The antimuscarinic potencies of the antagonists at Mb M2 and M 3 receptors (pArvalues, Table 1) werein good agreement with their affinity estimates determined in radioligand binding studies (Lazareno and Roberts 1989;Waelbroeck et al 1989) and previous functional studies (Barlow et al 1976;Gilani and Cobbin 1986;Micheletti et al 1987;Eltze 1988;Eltze et al 1988;Waelbroeck et al 1989;. A comparison of these affinity values with those determined at uterine muscarinic receptors suggests that the muscarinic receptor mediating contractions of the guinea-pig uterus is pharmacologically unique ( Table 1 ).…”

“…They can be distinguished by the use of selective antagonists such as methoctramine and AF-DX 116 (M 2 > M 1 > M 3 ) (Melchiorre et al 1987;Hammer et al 1986;Micheletti et al 1987), himbacine (M 1 ~ M 2 > M 3 ) (Gilani and Cobbin 1986;Lazareno and Roberts 1989), sila-hexocyclium (M 1 ~ M 3 > M 2 ) Waelbroeck et al 1989), 4-DAMP and hexahydro-sila-difenidol (M 3 ::? :: M 1 > M 2 ) (Barlow et al 1976;Mutschier and Lambrecht 1984;.…”

The Size of Hydroxyl Groups in Solution and the Changes in Size Associated With the Ionization of Phenolic, Carboxylic and Amino Groups in Phenolic Quaternary Ammonium Salts, Nicotine and Some Amino Acids: Possible Implications for Drug‐water and Drug‐receptor Interactions

“…For the binding of antagonists to muscarine-sensitive acetylcholine receptors it appears that for most drugs studied there is an increase in entropy (Barlow, Berry, Glenton, Nikolaou & Soh, 1976;Barlow & Burston, 1979;, though there is some evidence that with (-) forms of hyoscine and hyoscyamine the entropy of binding is negative (this was found with experiments involving intact preparations but not with those with isolated receptors).…”

Temperature Coefficients of Affinity Constants for the Binding of Antagonists to Muscarinic Receptors in the Rat Cerebral Cortex

“…For the phenylcyclohexylglycollic esters of triethylcholine and for the (+)-ester of choline the values are, within the limits of error, similar to those with the ileum. With the (-)-ester of choline the values are greatly different (+ 18 compared with +4) and similarly with methylatropine (+ 10 compared with -16) and with methylscopolamine (+9 compared with -22) (Barlow et al, 1976). In each of these instances binding to the receptors on the frag- Abramson, Barlow, Franks & Pearson, 1974;Barlow & Burston, 1979 and Hulme et al, 1978. t Values interpolated from measurements at 0°, 30', 37"C.…”

“…The effects of temperature on the affinity of binding of muscarinic antagonists can be studied only over a very narrow range with intact preparations producing a mechanical response, such as the guinea-pig ileum, because the contractions of the tissue are very sluggish below 30°C (Barlow, Berry, Glenton, Nikolau & Soh, 1976; Barlow & Burston, 1979). There is therefore considerable uncertainty attached to these estimates of the temperature coefficient.…”