The gastrin cholecystokinin (CCK) receptors mediating stimulation of acid secretion in rat isolated gastric mucosa (RGM) and contraction in guinea-pig isolated ileum longitudinal muscle-myenteric plexus (GPI) have been characterized by use of peptide agonists and the non-peptide antagonists, lorglumide, devazepide and L-365,260. 2. In RGM, gastrin peptides (sulphated gastrin heptadecapeptide (G-17), non-sulphated (ns) G-17 and pentagastrin) were potent agonists of acid secretion (EC50 values of 4.3, 16 and 27 nM respectively). Sulphated CCK octapeptide (CCK-8) was also a potent agonist, (EC50 = 0.9 nM), but was less efficacious, producing a lower maximal response. In contrast, in GPI, CCK-8 was a potent full agonist (EC50 = 1.4 nM) and was more than 1000 times more potent than the gastrin peptides in producing a sustained contractile response. 3. In GPI, CCK-8 (0.1 to 100 nM) produced sustained contractile responses, whilst CCK-4 (3 to 1000 nM) produced transient responses. These responses had different sensitivities to atropine (1 microM), suggesting that more than one receptor may mediate contraction in this tissue. 4. In RGM, L-365,260 was the most potent antagonist of pentagastrin-stimulated acid secretion (pA2 = 7.6). This functional affinity estimate was similar to that for L-365,260 as an antagonist of excitatory responses in rat ventromedial hypothalamic slices (Kemp et al., 1989) but differed from binding affinity estimates in guinea-pig cortex and gastric glands (Freidinger, 1989). 5. In GPI, devazepide, L-365,260 and lorglumide yielded different affinity estimates when compared against CCK-8 and CCK-4 or pentagastrin respectively.These studies were consistent with the view that the sustained response produced by CCK-8 was mediated by CCKA receptors and the transient response produced by CCK-4 and pentagastrin was mediated by CCKB receptors.6. Affinity estimates for L-365,260 and lorglumide against CCK-4 or pentagastrin in GPI were significantly different from corresponding estimates against pentagastrin in RGM. These studies are consistent with the view that gastrin/CCKB receptors in GPI may differ from those in RGM.
