ROLE OF MAST-CELL-DERIVED AND NON-MAST-CELL-DERIVED INFLAMMATORY MEDIATORS IN IMMUNOLOGICAL INDUCTION OF SYNAPTIC PLASTICITY

We have previously discovered a long-lasting enhancement of synaptic t ransmission in mammal autonomic ganglia caused by immunological activa tion of ganglionic mast cells. Subsequent to mast cell activation, lip id and peptide mediators are released which may modulate synaptic func tion. In this study we determined whether some mast cell-derived media tors, prostaglandin D-2 (PGD(2); 1.0 mu M), platelet aggregating facto r (PAF; 0.3 mu M) and U44619 (a thromboxane analogue; 1.0 mu M), and a lso endothelin-l (ET-1;0.5 mu M) induce synaptic potentiation in the g uinea pig superior cervical ganglion (SCG), and compared their effects on synaptic transmission with those induced by a sensitizing antigen, ovalbumin (OVA; 10 mu g/ml). The experiments were carried out on SCGs isolated from adult male guinea pigs (200-250 g) actively sensitized to OVA, maintained in oxygenated Locke solution at 37 degrees C. Synap tic potentiation was measured through alterations of the integral of t he post-ganglionic compound action potential (CAP). All agents tested caused long-term (LTP; duration greater than or equal to 30 min) or sh ort-term (STP; <30 min) potentiation of synaptic efficacy, as measured by the increase in the integral of the post-ganglionic CAP. The magni tude of mediator-induced potentiation was never the same as the antige n-induced long-term potentiation (A-LTP). The agent that best mimicked the antigen was PGD(2), which induced a 75% increase in CAP integral for LTP (antigen: 94%) and a 34% increase for STP (antigen: 91%). PAF- , U44619-, and ET-l-induced increases in CAP integral ranged for LTP f rom 34 to 47%, and for STP from 0 to 26%. These results suggest that t he agents investigated may participate in the induction of A-LTP.