ANALYSIS OF THE CCKB RECEPTOR ANTAGONISM OF VIRGINIAMYCIN IN GUINEA-PIG ILEUM LONGITUDINAL MYENTERIC PLEXUS

1 Virginiamycin, a macrolide reported to bind selectively to CCK(B)/gastrin receptors has been studied in a functional test, namely cholecystokinin-induced contraction of guinea-pig ileum myenteric plexus (LMMP). 2 Virginiamycin (1-10 muM) antagonized the selective CCK(B) agonist cholecystokinin tetrapeptide (CCK-4). The antagonism appeared not to be competitive as the highest concentration (10 muM) caused a reduction of its maximal effect. An apparent pA2 of 6.64 +/- 0.06 (s.e.) could be estimated if this depression was ignored. The selective CCK(B) antagonist, L-365,260 (0.01-0.3 muM) antagonized competitively the CCK-4 induced contraction and a pK(B) of 8.60 +/- 0.16 (s.e.) was estimated. 3 The combined dose-ratio analysis for virginiamycin, tested at 3 and 10 muM in association with 0.03 and 0.1 muM L-365,260, respectively, resulted in observed log dose-ratios of 1.39 and 1.53. That was consistent with both antagonists acting on the same receptor in LMMP. 4 These data, represent the first evidence of the antagonism of virginiamycin in a functional assay and they support the hypothesis of homogeneity between CCK(B) receptors in the CNS and in peripheral tissues.