High impact information on 3-[[(1R)-2-[[(2R)-3-indolin-3-yl-2-methyl-2-[[(1S,4S)-1,7,7-trimethylnorbornan-2-yl]oxycarbonylamino]propanoyl]amino]-1-phenyl-ethyl]carbamoyl]propanoic acid

• In addition, Fos immunohistochemistry was performed in rats (n=3-4) treated with CCK-8s (1 microg) alone or in combination with PD 135158 (0.1 microg) [1].
• Furthermore, in contrast to the clear anxiolytic profile of diazepam (1 mg/kg), and despite the comprehensive behavioural profiles yielded by ethological analysis, all three CCK receptor antagonists studied (devazepide, L-365, 260 and PD 135158) were found to be without significant effect under present test conditions [2].
• PD-135158, a CCKB receptor antagonist, microinjected into the nucleus accumbens and the expression of conditioned rewarded behavior [3].
• The CCKB antagonist PD 135158 reduced the CCK effects in 10 of 14 cells; the CCKA antagonist KL 1001 reduced the CCK effects in 17 of 36 cells [4].
• These data demonstrate that the CCKB/gastrin receptor antagonist, PD 135158, acts as a full agonist at the rat pancreatic CCKA receptor [5].

Biological context of 3-[[(1R)-2-[[(2R)-3-indolin-3-yl-2-methyl-2-[[(1S,4S)-1,7,7-trimethylnorbornan-2-yl]oxycarbonylamino]propanoyl]amino]-1-phenyl-ethyl]carbamoyl]propanoic acid

• To investigate the role of cholecystokininB (CCKB) receptors in the brain in the control of food intake, we administered PD-135158, a specific and potent CCKB antagonist, into the lateral ventricle of male, Sprague-Dawley rats 30 min before a 60-min intake test [6].

Anatomical context of 3-[[(1R)-2-[[(2R)-3-indolin-3-yl-2-methyl-2-[[(1S,4S)-1,7,7-trimethylnorbornan-2-yl]oxycarbonylamino]propanoyl]amino]-1-phenyl-ethyl]carbamoyl]propanoic acid

• SR 27897 (but not PD 135158) inhibited the preprandial phase and greatly reduced postprandial pancreatic juice and enzyme outflows [7].

Associations of 3-[[(1R)-2-[[(2R)-3-indolin-3-yl-2-methyl-2-[[(1S,4S)-1,7,7-trimethylnorbornan-2-yl]oxycarbonylamino]propanoyl]amino]-1-phenyl-ethyl]carbamoyl]propanoic acid with other chemical compounds

• For this purpose we used L 364718 a selective antagonist for CCKA R and PD 135158 a selective antagonist for CCKB R [8].

Gene context of 3-[[(1R)-2-[[(2R)-3-indolin-3-yl-2-methyl-2-[[(1S,4S)-1,7,7-trimethylnorbornan-2-yl]oxycarbonylamino]propanoyl]amino]-1-phenyl-ethyl]carbamoyl]propanoic acid

• The CCKB/gastrin receptor antagonist, PD 135158 (CAM 1028), surprisingly stimulates lipase release from isolated rat pancreatic acini dose dependently in a biphasic manner, with identical efficacy but lower potency compared to cholecystokinin octapeptide (CCK-8) [5].
• The first objective was studied by suppressing external stimuli associated with food intake (unexpected meal) and the second by infusing highly specific and potent antagonists of CCK-A (SR 27897) and CCK-B/gastrin (PD 135158) receptors during the prandial period [7].
• PD 135158, a CCKB/gastrin receptor antagonist, stimulates rat pancreatic enzyme secretion as a CCKA receptor agonist [5].
• Specific CCK-A and CCK-B/G receptor antagonists (SR 27897 and PD 135158, respectively) were used to identify the CCK receptor subtype involved in exogenous CCK- and gastrin-induced exocrine pancreatic responses [9].

Analytical, diagnostic and therapeutic context of 3-[[(1R)-2-[[(2R)-3-indolin-3-yl-2-methyl-2-[[(1S,4S)-1,7,7-trimethylnorbornan-2-yl]oxycarbonylamino]propanoyl]amino]-1-phenyl-ethyl]carbamoyl]propanoic acid

• The present experiment examines whether the blockade of CCKB receptors in the NAC with microinjection of PD-135158 (10 micrograms in 0.5 microliter) potentiates bar-pressing for stimuli previously associated with food reward [3].

References