Dynorphin binds to neuropeptide Y and peptide YY receptors in human neuroblastoma cell lines.
The modulation of neuropeptide Y (NPY) and peptide YY (PYY) receptors by dynorphin, luteinizing hormone-releasing hormone (LHRH), corticotropin-releasing factor (CRF), and cholecystokinin octapeptide has been studied in human neuroblastoma cell lines SK-N-MC and SMS-MSN, which express Y1 and Y2 receptors for NPY/PYY. Dynorphin A and LHRH inhibited the binding of NPY/PYY to SK-N-MC cell membranes at concentrations ranging from 10(-7) to 10(-5) M, whereas dynorphin A and CRF were effective in SMS-MSN cells. The inhibitory effect of dynorphin A on NPY/PYY binding was observed in the presence of guanosine 5'-O-(3-thiotriphosphate), a nonhydrolyzable GTP analogue, as well as H-7 and H-8, novel inhibitors of protein kinases C and A. However, U-50488, the most potent kappa-selective compound did not mimic the dynorphin action. Dynorphin A showed neither effect on the dissociation of NPY/PYY from their receptors nor inhibition on the basal as well as forskolin-stimulated adenosine 3',5'-cyclic monophosphate response. These results indicate that the interaction of dynorphin A with Y1 and Y2 receptors is not mediated by changes in receptor-G protein interaction, receptor phosphorylation, and allosteric binding to NPY/PYY receptors but that dynorphin A binds to NPY/PYY receptors at high concentrations, probably in an antagonistic manner.
Miura
M
M
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Inui
A
A
Sano
K
K
Ueno
N
N
Teranishi
A
A
Hirosue
Y
Y
Nakajima
M
M
Okita
M
M
Togami
J
J
Koshiya
K
K
D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D004399:Dynorphins / Q000378:metabolism* / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D047428:Protein Kinase Inhibitors; D011964:Receptors, Gastrointestinal Hormone / Q000187:drug effects / Q000378:metabolism*; D017476:Receptors, Neuropeptide Y / Q000187:drug effects / Q000378:metabolism*; D012844:Sincalide / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D047428:Protein Kinase Inhibitors; D011964:Receptors, Gastrointestinal Hormone; D017476:Receptors, Neuropeptide Y; C082172:peptide YY receptor; D007987:Gonadotropin-Releasing Hormone; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D004399:Dynorphins; D003346:Corticotropin-Releasing Hormone; D012844:Sincalide