Phosphorylation of synapsin I and dynamin in rat forebrain synaptosomes: modulation by sigma (sigma) ligands.
The effects of sigma (sigma) ligands on protein phosphorylation were examined in crude, rat forebrain synaptosomes. Synaptosomes were prelabelled with 32P(i) and incubated with the sigma ligands 1,3-di-o-tolylguanidine (DTG), (+)pentazocine and (-)pentazocine (3, 10, 30, 100, 300 microM), or haloperidol, reduced haloperidol, and (+)SKF 10,047 (100 microM). Aliquots were then incubated for 10 s in control (5 mM K+) or depolarising buffer (41 mM K+). All the sigma ligands increased basal phosphorylation of synapsin Ib and other proteins including dynamin, and inhibited the depolarisation-dependent increase in phosphorylation of synapsin Ib in synaptosomes. The effects of these ligands are not directly on protein kinases or protein phosphatases. This indicates that the sigma ligands are mediating their effects via interaction with sigma binding sites, and suggest, for the first time, that protein phosphorylation may be one mechanism through which sigma ligands produce their biological effects.
Brent
P J
PJ
Neuroscience Group, Faculty of Medicine, University of Newcastle, Mater Hospital, Waratah, N.S.W., Australia.
Haynes
H
H
Jarvie
P E
PE
Mudge
L
L
Sim
A T
AT
Dunkley
P R
PR
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D008870:Microtubules / Q000378:metabolism*; D010423:Pentazocine / Q000494:pharmacology; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D010766:Phosphorylation; D016548:Prosencephalon / Q000378:metabolism*; D051381:Rats; D017480:Receptors, sigma / Q000378:metabolism*; D016704:Synapsins / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism*
D000927:Anticonvulsants; D006146:Guanidines; D017480:Receptors, sigma; D016704:Synapsins; C012134:SK&F 10047; D020558:GTP Phosphohydrolases; D034281:Dynamins; D010620:Phenazocine; D006220:Haloperidol; C050232:1,3-ditolylguanidine; D010423:Pentazocine