gastrins and cholecystokinin-9

The effect of luminal gastrin on the secretion of pancreatic juice was studied in seven conscious preruminant calves employing luminal infusions of gastrin and cholecystokinin (CCK)-9 and pharmacological CCK1 and CCK2 receptor blocks with antagonists. The study was performed in the preprandial and prandial states. Pharmacological blocking of the CCK2 receptor, like that of the CCK1 receptor, resulted in reduction of pancreatic postprandial secretion and increased the duration of the prandial pattern of duodenal electrical activity. Exogenous luminal gastrin, like luminal CCK-9, enhanced the secretion of pancreatic juice proteins, though the overall effect of gastrin was weaker than that of CCK-9. The effect was inhibited by infusion of CCK2 but also by CCK1 receptor antagonist. In conclusion, duodenal luminal gastrin can stimulate exocrine pancreatic secretion by a mechanism that depends on CCK2 receptors in calves. Involvement of the CCK1 receptor in this mechanism needs further investigation. Prandial pancreatic secretory and duodenal motility cycles can be regulated by endogenous gastrin release.

Topics: Animals; Anti-Anxiety Agents; Cattle; Cholecystokinin; Duodenum; Gastrins; Gastrointestinal Motility; Hormone Antagonists; Indoleacetic Acids; Indoles; Infusion Pumps; Infusions, Parenteral; Meglumine; Pancreas; Peptide Fragments; Receptor, Cholecystokinin A; Receptor, Cholecystokinin B; Thiazoles

N-terminal lipophilic derivatization of the fully active cholecystokinin analogue (Thr,Nle)-CCK-9 with the di-myristoyl-raz-thioglyceryl moiety leads to spontaneous self-aggregation of the lipopeptide into polydispersed vesicles at the liquid state. The high degree of fluidification of the vesicles favors a fast and net transfer of monomers to phospholipid bilayers even below the phase-transition temperature of the acceptor vesicles. Surprisingly, the process is accompanied by formation of peptide clusters. The peptide-rich domains exhibit a high affinity for Ca2+, a fact which may be correlated to the biological function of CCK as this hormone is known to stimulate calcium outflux from reserves in the cell membranes. Moreover, induced membrane affinity allowed to study more precisely the interaction of the CCK peptide with lipid bilayers as mimicry of cell membranes. Differently from what was observed with a similar lipogastrin derivative in which the peptide tail was found to be permanently exposed to the aqueous phase, in the case of the lipo-CCK compound insertion of its C-terminal active site into more hydrophobic compartments of the bilayer is occurring, as well as a folding into beta-type structures, thus confirming the role of cell membranes in displaying peptide hormones for specific receptor recognition.

Topics: Amino Acid Sequence; Calcium; Cell Membrane; Cholecystokinin; Circular Dichroism; Dimyristoylphosphatidylcholine; Gastrins; Lipid Bilayers; Molecular Sequence Data; Peptide Fragments; Phospholipids; Protein Conformation; Tryptophan

The effect of cholecystokinin (CCK)-gastrin family peptides (caerulein, unsulfated gastrin-17, and pentagastrin) and secretin in activating amiloride-sensitive 22Na uptake were investigated in guinea pig pancreatic acini. Secretin had no effect, but CCK-gastrin peptides stimulated the amiloride-sensitive 22Na uptake. The effect of caerulein was inhibited by dibutyryl guanosine 3',5'-cyclic monophosphate (cGMP) and asperlicin, indicating that activation of the Na+-H+ antiport caused by caerulein is mediated by CCK receptors. The effect of gastrin was dibutyryl cGMP and asperlicin insensitive, whereas the effect of pentagastrin was inhibited by the CCK antagonists but with a low affinity, indicating that the effect of gastrin and that of pentagastrin was CCK receptor independent. The calcium ionophore A23187 caused an increase in amiloride-sensitive 22Na uptake. However, the effect of caerulein, which increased internal calcium concentration, was not modified after depletion of intracellular calcium, and that of CCK-gastrin family peptides was not dependent on external calcium concentration. Activation of amiloride-sensitive 22Na uptake was also induced by 12-O-tetradecanoylphorbol 13-acetate and 1-oleoyl-2-acetyl-glycerol. Activation of protein kinase c may be involved in the mechanism of caerulein or gastrin in activating the Na+-H+ exchange.

Topics: Amiloride; Amylases; Animals; Calcimycin; Calcium; Cholecystokinin; Diglycerides; Gastrins; Guinea Pigs; Hydrogen; Ion Exchange; Pancreas; Peptide Fragments; Peptides; Phorbol Esters; Secretin; Sodium; Tetradecanoylphorbol Acetate

(Thr28,Nle31)CCK(23-33) (CCK-9) and gastrin(1-17)I (gastrin) inhibited adenylate cyclase activity in membranes from the tumoral rat pancreatic acinar cell line AR 4-2J through a Bordetella pertussis toxin-sensitive mechanism. This contrasted with the stimulatory effect exerted by CCK-9 on adenylate cyclase activity in membranes from normal rat pancreas. The relative potency of CCK-9, gastrin, and related peptides in inhibiting adenylate cyclase, when confronted with previous evidence, suggests that 'non-selective CCK-gastrin CCK-B receptors' predominating over 'selective CCK-A receptors' in the AR 4-2J cell line, favored the coupling of the first receptors to adenylate cyclase through Gi, while CCK-A receptors capable of stimulating the enzyme through Gs were detected only after Bordetella pertussis toxin pretreatment.

Topics: Adenylate Cyclase Toxin; Adenylyl Cyclase Inhibitors; Animals; Cell Membrane; Cholecystokinin; Gastrins; Guanosine Triphosphate; Pancreas; Pancreatic Neoplasms; Pentagastrin; Peptide Fragments; Pertussis Toxin; Rats; Secretin; Tetragastrin; Tumor Cells, Cultured; Vasoactive Intestinal Peptide; Virulence Factors, Bordetella