Different affinity states of CCK1 receptors on pancreatic acini and gastric smooth muscle in the rat

It has recently been shown that-after chronic cholecystokinin (CCK) treatme nt-an adaptation of pancreatic secretory but not gastric motor function doe s occur. Recent studies indicate that the CCK1-receptor exists in two (i.e. high and low) affinity states, which could be distinguished by the CCK-ana logue JMV-180. CCK occupancy of high and low affinity sites is thought to b e related to the initiation of different intracellular events and consequen t biological responses. Affinity states of CCK1-receptors on pancreas and g astrointestinal (GI) smooth muscle could be different and this can offer an explanation for the different effects of CCK on pancreatic and gastric gro wth. We therefore studied the affinity states of CCK1-receptors on isolated rat pancreatic acini and gastric smooth muscle preparations. When acini we re incubated with increasing concentrations of CCK-8, a biphasic (i.e. stim ulation followed by inhibition) effect on amylase release was observed. JMV -180 caused only stimulation of enzyme release and combined JMV-180 and CCK stimulation (at submaximal doses) resulted in an additive secretory respon se. CCK-8 induced contractions of pyloric, antral and fundic muscle in a co ncentration-dependent manner. The response was monophasic, reaching a plate au. JMV-180 had only a very weak effect on these preparations. On the contr ary, it inhibited CCK-induced contractions in a competitive manner, the con centration-response curve to CCK being shifted to the right by the CCK anal ogue. Our data suggest that the affinity states of CCK1-receptors on rat pa ncreatic and gastric tissue are different. On pancreatic acini CCK1-recepto rs exist in both high- and low-affinity states whose occupation is followed by the sequence of intracellular events leading to growth. In contrast, oc cupation of low affinity receptors (the only ones present in the GI smooth muscle) does not lead to cell proliferation. This difference therefore expl ains the different adaptive response of the pancreas and the stomach to chr onic CCK administration. Furthermore, different affinity states of CCK1-rec eptors may mediate different functions of the digestive tract. (C) 2001 Els evier Science Ltd. All rights reserved.