Arachidonic acid closes gap junction channels in rat lacrimal glands.
The effects of arachidonic acid (AA) on gap junction conductance of rat lacrimal glands have been studied with the double patch-clamp technique. Extracellular application of 50-100 microM AA for a few minutes induced a closure of gap junction channels. This effect was mimicked by linoleic acid and by other non-degradable fatty acids (myristic and lauric), and was not blocked by inhibitors of AA metabolism. This suggests that the active molecule was the fatty acid itself, and not one of its oxidative derivatives. Inhibitors of AA metabolism caused a certain degree of uncoupling by themselves, probably due to the accumulation of AA. This effect was reduced in the presence of 10 microM 4-bromophenacylbromide, an inhibitor of phospholipase A2. The effect of AA did not seem to be mediated by an increase of intracellular Ca concentration, nor by a change in the activity of guanylate or adenylate cyclases, nor by activation of protein kinase C. Therefore it could be attributed to a direct effect of AA on gap junctions. Analysis of single gap junction channel currents showed that AA-induced closure of these channels resulted from a change in the number of open channels, and not from a reduction of their conductance. Finally, acetylcholine-induced closure of gap junction channels was not primarily mediated by an increase in AA concentration, although such an increase may well follow the activation of muscarinic receptors and play a role in the acetylcholine effect.
Giaume
C
C
Laboratoire de Neurobiologie, Ecole Normale Supérieure, Paris, France.
Randriamampita
C
C
Trautmann
A
A
D000098:Acetophenones / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D004553:Electric Conductivity; D005227:Fatty Acids / Q000494:pharmacology; D007365:Intercellular Junctions / Q000187:drug effects* / Q000502:physiology; D007765:Lacrimal Apparatus / Q000187:drug effects* / Q000502:physiology; D010084:Oxidation-Reduction; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats
D000098:Acetophenones; D001095:Arachidonic Acids; D005227:Fatty Acids; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D000109:Acetylcholine; C006821:4-bromophenacyl bromide