M. Miura et al., DYNORPHIN BINDS TO NEUROPEPTIDE-Y AND PEPTIDE YY RECEPTORS IN HUMAN NEUROBLASTOMA CELL-LINES, American journal of physiology: endocrinology and metabolism, 30(5), 1994, pp. 702-709
The modulation of neuropeptide Y (NPY) and peptide YY (PYY) receptors
by dynorphin, luteinizing hormone-releasing hormone (LHRH), corticotro
pin-releasing factor (CRF), and cholecystokinin octapeptide has been s
tudied in human neuroblastoma cell lines SK-N-MC and SMS-MSN, which ex
press Y-1 and Y-2 receptors for NPY/PYY. Dynorphin A and LHRH inhibite
d the binding of NPY/PYY to SK-N-MC cell membranes at concentrations r
anging from 10(-7) to 10(-5) M, whereas dynorphin A and CRF were effec
tive in SMS-MSN cells. The inhibitory effect of dynorphin A on NPY/PYY
binding was observed in the presence of guanosine 5'-O-(3-thiotriphos
phate), 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 pote
nt kappa-selective compound did not mimic the dynorphin action. Dynorp
hin A showed neither effect on the dissociation of NPY/PYY from their
receptors nor inhibition on the basal as well as forskolinstimulated a
denosine 3',5'-cyclic monophosphate response. These results indicate t
hat the interaction of dynorphin A with Y-1 and Y-2 receptors is not m
ediated by changes in receptor-G protein interaction, receptor phospho
rylation, and allosteric binding to NPY/PYY receptors but that dynorph
in A binds to NPY/PYY receptors at high concentrations, probably in an
antagonistic manner.