1. Cholecystokinin-induced protection of cultured cortical neurons against glutamate neurotoxicity
K Ozaki, Y Sato, Y Tamura, S Miura, R Matsuoka, T Yoshinaga, A Akaike Brain Res . 1991 Aug 23;557(1-2):303-7. doi: 10.1016/0006-8993(91)90149-p.
The effects of cholecystokinin (CCK) on glutamate-induced neurotoxicity were examined using cultured rat cortical neurons. Brief exposure of glutamate followed by an incubation with normal solution for more than 60 min reduced cell viability by 60-70%, compared with control values. Glutamate-induced neurotoxicity was significantly inhibited by MK-801 and ketamine, which are non-competitive blockers of N-methyl-D-aspartate (NMDA) receptors. Octapeptide CCK-8S and CCK-related decapeptide ceruletide at concentrations of 10(-9)-10(-7) M dose-dependently reduced glutamate-induced neurotoxicity. A desulfated analog CCK-8NS, which acts selectively as an antagonist of CCKB receptors, also reduced glutamate neurotoxicity. The neuroprotective effects of CCK were antagonized by L-365260, a CCKB receptor antagonist, but not by L-364718, a CCKA receptor antagonist. These results suggest that CCK protects cortical neurons against NMDA receptor-mediated glutamate neurotoxicity via CCKB receptors.
2. Negative ion electrospray mass spectra of caerulein peptides: an aid to structural determination
Craig S Brinkworth, Michael J Tyler, Paul F Alewood, Paul A Wabnitz, John H Bowie, Pinmanee Boontheung Rapid Commun Mass Spectrom . 2002;16(4):281-6. doi: 10.1002/rcm.577.
MS/MS data derived from the [M-H](-) ions of desulfated caerulein peptides provide (i) sequencing information from a combination of alpha, beta and gamma backbone cleavages, and (ii) identification of specific amino acid side chains by side-chain cleavages [e.g. Ser (-CH(2)O), Thr (-CH(3)CHO) and Asp (-H(2)O)] (fragmentations having no counterparts in positive ion spectra). In addition, delta and/or gamma backbone cleavage ions from Asp residues identify the position of these residues in the peptide. In contrast, neither delta nor gamma cleavage ions are observed from either the Gln2 residue nor from Phe residues. Full structural information can be obtained from a consideration of the positive and negative ion MS/MS data in concert.
3. Effects of caerulein-related peptides on cholecystokinin receptor bindings in brain and pancreas
K Igano, M Fujimoto, K Inouye, I Irie, T Okabayashi, K Watanabe Biochem Pharmacol . 1985 Apr 1;34(7):1103-7. doi: 10.1016/0006-2952(85)90616-1.
A number of caerulein (CLN)-related peptides were synthesized and compared in terms of their affinities for cholecystokinin (CCK) receptors. We have found that these peptides can be classified into three types according to their relative affinities for the brain and pancreatic receptors. The first group (type A) of peptides includes CLN and analogs retaining the Tyr(SO3H)4 residue and the COOH-terminal amide group. Type A peptides were as potent as CLN in inhibiting [125I]BH-CCK-8 binding and showed almost the same affinities for pancreatic and brain receptors. When the Tyr(SO3H)4 residue was either deleted or desulfated (type B), the affinities of the peptides decreased remarkably for the pancreatic receptors but much less for the brain receptors. The type C peptides were deamidated, oxidized, or shortened in the COOH-terminal region and exhibited greatly decreased affinities for both brain and pancreatic receptors but a much greater decrease for the brain receptor. These results indicate that, although the Tyr(SO3H)4 residue and the COOH-terminal structure are both essential for CLN to bind to the CCK receptors, the former is of critical importance for the binding to the pancreas and the latter is rather important for the binding to the brain.
