PHORBOL ESTERS ALTER THE MORPHOLOGY OF CULTURED GUINEA-PIG MYENTERIC GLIA VIA PROTEIN-KINASE C-INDEPENDENT MECHANISM

Cultures of myenteric ganglia from adult guinea-pigs were used to stud y the influence of neuroactive substances on glial cells by monitoring changes in their morphology. The following substances had no effect o n glial morphology: adenosine, ATP, carbachol, glutamate, bradykinin, isoprenaline, prostaglandin E-2, sodium nitroprusside and lipopolysacc haride. The only substances found to affect glial morphology were phor bol esters, and in particular phorbol 12-myrisate 13-acetate (PMA), wh ich acted at the nM range. Glial cells, which were normally polygonal, assumed a stellate shape within 30-60 min after the addition of PMA. Protein kinase C (PKC) inhibitors did not block this effect, and PKC a ctivators did not mimic it. The effect of PMA was also not mediated by changes in the intracellular concentrations of either Ca2+, H+ or cyc lic AMP. Dye coupling among glial cells was blocked by PMA. The phorbo l ester-mediated effect on glial structure may have profound influence on neuronal organization and function. (C) 1997 Elsevier Science Irel and Ltd.