Neurite outgrowth-stimulating activities of beta-casomorphins in Neuro-2a mouse neuroblastoma cells.
Endogenous opioid peptides and opiate drugs are known to affect the development of the nervous system. beta-Casomorphins (beta-CMs) belong to a family of exogenous opioid peptides derived from the milk protein beta-casein by proteolytic fragmentation. We investigated the effects of various fragments and analogues of beta-CM on neurite outgrowth in Neuro-2a mouse neuroblastoma cells. The fragments beta-CM-5 to -9 and beta-CM-5 amide stimulated neurite outgrowth. Fragments shorter than beta-CM-5 (beta-CM-3, -4, and beta-CM-4 amide) and longer than beta-CM-9 (beta-CM-13 and -21) had no effects. The activity of beta-CMs to promote neurite outgrowth does not correlate with their opioid activity in guinea-pig ileum. The effect of the most potent fragment, beta-CM-5, was prevented by the micro-opioid receptor-selective antagonist D-Phe-Cys(2)-Tyr(3)-D-Trp-Orn(5)-Thr(6)-Pen(7)-Thr(8)-NH(2) (CTOP), or by pretreatment with pertussis toxin. These results suggest that the stimulatory effects of beta-CMs on neurite outgrowth were mediated through G protein-coupled micro-opioid receptors.
Sakaguchi
Minoru
M
Laboratory of Cell Biology, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan. sakaguti@gly.oups.ac.jp
Murayama
Kouichi
K
Jinsmaa
Yunden
Y
Yoshikawa
Masaaki
M
Matsumura
Eiko
E
D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology*; D002364:Caseins / Q000737:chemistry; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D004723:Endorphins / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism / Q000502:physiology; D051379:Mice; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D009447:Neuroblastoma / Q000473:pathology*; D010446:Peptide Fragments / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D010802:Phylogeny; D017450:Receptors, Opioid, mu / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002364:Caseins; D004723:Endorphins; D010446:Peptide Fragments; D017450:Receptors, Opioid, mu; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D013004:Somatostatin; C021968:beta-casomorphins; D000242:Cyclic AMP; D037342:Pertussis Toxin