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 e xamined in crude, rat forebrain synaptosomes. Synaptosomes were prelab elled with P-32(i) and incubated with the sigma ligands 1,3-di-o-tolyl guanidine (DTG), (+)pentazocine and (-)pentazocine (3, 10, 30, 100, 30 0 mu M), or haloperidol, reduced haloperidol, and (+)SKF 10,047 (100 m u M). Aliquots were then incubated for 10 s in control (5 mM K+) or de polarising buffer (41 mM K+). All the sigma ligands increased basal ph osphorylation 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 dir ectly on protein kinases or protein phosphatases. This indicates that the sigma ligands are mediating their effects via interaction with a b inding sites, and suggest, for the first time, that protein phosphoryl ation may be one mechanism through which sigma ligands produce their b iological effects.