Pharmacological and biochemical evidence for the simultaneous expression of CCK_B/gastrin and CCK_A receptors in the pig pancreas

Abstract

In the pig, the secretory response of the pancreas is not inhibited by the antagonist MK329 suggesting that cholecystokininA (CCKA) receptors are not involved. Membranes were isolated from the pancreas of 6 Large White pigs to characterize their CCK receptors. The binding of [M125I]‐BH‐[Thr, Nle]CCK‐9 was dependent on pH, maximal after a 90 min incubation period, saturable and reversible. Saturation analysis of the binding demonstrated a single class of high affinity sites (Kd = 0.22 ± 0.02 nM) and a binding capacity, Bmax= 110.64±12.50 fmol mg−1 protein. Competition binding by agonists and antagonists of CCKA and CCKB/gastrin receptors demonstrated the presence of two distinct binding components, sites presenting a high affinity for [Thr, Nle]CCK‐9, gastrin, PD 135158, L‐365,260 and a low affinity for MK329, SR 27897, and sites presenting a high affinity for [Thr, Nle]CCK‐9, MK329, SR 27897 and a low affinity for gastrin, PD 135158, L‐365,260. These pharmacological data demonstrate the presence of both CCKA and CCKB/gastrin receptors in the pig pancreas, the latter being predominant. Two distinct membrane proteins (50 and 85–100 kDa, respectively) display pharmacological features of CCKB/gastrin and CCKA receptors. In pigs, as in calves and humans, CCKB/gastrin receptors are predominant in the pancreas.

Cholecystokinin and Gastrin Receptors

“…CCK and gastrin stimulate pancreatic secretion in calves via both CCK1R and CCK2R but CCK1R, although not predominantly expressed, seems to play a major role (272). CCK2R was also found to predominate in the pig pancreas where a proportion of 70% CCK2R and 30% CCK1R was estimated; however, the functional role of CCK2R in pig pancreatic secretion remains uncertain (146,279,375). These data raise the question of which functions are under the control of the CCK2R in the exocrine pancreas.…”

Gastrin, cholecystokinin and gastrointestinal tract functions in mammals

“…The presence of CCK 2 receptors in the pancreas was firstly observed in the calf (Le Meuth et al 1993;Desbois et al 1999) and then in the pig (Philippe et al 1997) by binding and photoaffinity labelling studies or by in situ hybridation and in man by storage phosphor autoradiography after radioligand binding to a tissue section . Similarly, amylase release from isolated pig acini in response to caerulein indicated stimulation in the nM range, a typical CCK 2 response not inhibited by the CCK 1 receptor antagonist MK-329 (Morisset et al 1996).…”

Three-Day Enteral Exposure to a Red Kidney Bean Lectin Preparation Enhances the Pancreatic Response to CCK Stimulation in Suckling Pigs

“…Therefore, the results implied that the effect of CCK on stimulating exocrine fl uid secretion might have matured due to the lectin treatment, as seen naturally during the weaning process. This effect, however, is not likely to be mediated directly by the pancreatic duct cells, since CCK receptors have not been found on either the acinar or the ductal cells in pigs [22][23][24][25][26] . Another explanation might be that exposure to lectins stimulates the development of a regulatory pathway between the acinar and ductal cells.…”