Evidence for two cholecystokinin receptors mediating the contraction of the guinea pig isolated ileum longitudinal muscle myenteric plexus.

ABSTRACT

In guinea pig isolated ileum longitudinal muscle myenteric plexus, cholecystokinin octapeptide (CCK-8S) produced a rapid (phasic) contraction followed by a slower tonic phase. The tetrapeptide derivative CCK-4 and pentagastrin elicited only the phasic response up to 10(-6) M, whereas the tonic phase was also apparent at higher concentrations. The rank order of potency for the effect of agonists on the tonic and phasic responses were CCK-8S much greater than gastrin greater than CCK-8US congruent to pentagastrin greater than CCK-4 and CCK-8S greater than gastrin congruent to pentagastrin greater than CCK-4 greater than CCK-8US, respectively. Phasic responses of CCK-8S and CCK-4 were sensitive to atropine, whereas the tonic response could be completely abolished with the neurokinin-1 antagonist GR82334. The CCK-A receptor antagonist L-364,718 up to 10(-7) M had little effect on the phasic contracture of CCK-4. The CCK-B/gastrin receptor antagonist L-365,260 had no effect on the CCK-8S phasic response up to 10(-7) M, but antagonized the phasic response induced by low concentrations of CCK-4 in a competitive manner with an estimated pKB of 8.51. This value is close to that of 8.53 found in a guinea pig cortical binding assay. Both the second phase of the CCK-4 phasic concentration response curve (CRC) and the tonic contraction were insensitive to L-365,260.(ABSTRACT TRUNCATED AT 250 WORDS)