sincalide and cholecystokinin-33-(10-20)

1 Mechanical activity was recorded in isolated muscle preparations from the circular and longitudinal layers of different regions of canine stomach (16 dogs). At least eight muscle strips were excised from each stomach: longitudinal (lo) and circular (ci) strips from fundus (Fu), corpus (Co) and antrum (An), and circular strips from the inner and outer portion of the pyloric ring. 2 Cholecystokinin 33 (CCK 33), cholecystokinin octapeptide (CCK 8), caerulein and pentagastrin produced the same pattern of responses, with differences in their potencies: caerulein was 10 times more potent than CCK 8, and CCK eight to ten times more potent than CCK 33 and pentagastrin. 3 The most characteristic effect of the CCK peptides was an increase in frequency of the phasic activity of Fu-ci, Co and An preparations (threshold 10(-10) mol/l for CCK 8), usually combined with weak or moderate increases of amplitude. 4 Slight tonic activations were observed in Fu-lo, Co-lo and An-lo (around 10% of the ACH maximum), and stronger tonic activations in Fu-ci and Co-ci (around 50% of the ACH maximum). 5 No responses to CCK were seen in pyrolic preparations. 6 Experiments with receptor antagonists (adrenoceptors, muscarinic and histamine receptors), and with tetrodotoxin indicate that the peptides act by a direct effect on smooth muscle.

Topics: Animals; Ceruletide; Cholecystokinin; Dogs; Female; In Vitro Techniques; Male; Muscle Contraction; Muscle, Smooth; Pentagastrin; Peptide Fragments; Peptides; Sincalide; Stomach

In anesthetized rats, a marked decrease in CCK-OP activity and, to a far lesser extent, in the pancreatic secretory effect of CCK-33 were found after portal administration, compared to the femoral route. Changes in the biological activity of CCK-OP were further investigated after 30 min incubation with different subcellular liver fractions (1000 X g, 12,000 X g, microsomal fraction with or without NADPH). All the subcellular liver fractions caused an approximately 70% decrease in the CCK-effect, as calculated from dose-response relationships. The inactivation of CCK-OP after incubation with microsomal fractions of thioacetamide (TAA)-induced cirrhotic liver did not differ from that of control rats. The CCK-OP dose-response curves were similar in cirrhotic and control rats, but the pancreatic secretion was sustained to a greater extent and the inhibitory effect of supramaximal stimulation was delayed in cirrhotic rats. It was concluded that CCK-OP can be inactivated by liver proteins present in microsomal fractions, by a NADPH-independent mechanism. This inactivation did not diminish in liver cirrhosis. There were no changes in CCK-OP elimination in cirrhotic rats in vivo, thus pancreatic hypertrophy in experimental cirrhosis must be explained by other mechanisms.

Topics: Animals; Cholecystokinin; Female; Femoral Vein; In Vitro Techniques; Injections, Intravenous; Liver; Liver Cirrhosis, Experimental; Male; Microsomes, Liver; Pancreas; Peptide Fragments; Portal Vein; Proteins; Rats; Rats, Inbred Strains; Sincalide; Trypsin