4-AMINOPYRIDINE AND LOW CA2+ DIFFERENTIATE PRESYNAPTIC INHIBITION MEDIATED BY NEUROPEPTIDE-Y, BACLOFEN AND 2-CHLOROADENOSINE IN RAT HIPPOCAMPAL CA1 INVITRO

1 Presynaptic inhibition is mediated by several receptors at the stratum radiatum-CA1 synapse of rat hippocampus. We tested whether the same mechanism is activated by neuropeptide Y (NPY), baclofen and 2-chloroadenosine (2-CA), reasoning that if the receptors all activated the same process, then they should all respond to indirect manipulations of transmitter release in the same manner. 2 The effects on presynaptic inhibition by the potassium channel blocker, 4-aminopyridine (4-AP) and low extracellular concentrations of Ca2+ in the presence of 4-AP were compared using evoked population excitatory postsynaptic potentials (p.e.p.s.p.) responses in the rat hippocampal slice in vitro. 3 Log concentration-effect relationships for the inhibition of excitatory transmission were constructed for all 3 drugs in normal saline, and in the presence of 30 and 100-mu-M 4-AP. 4-AP reduced the inhibition mediated by all three substances, 100-mu-M 4-AP was only slightly more effective than 30-mu-M. 4 Lowering extracellular Ca2+ from 1.5 to 0.75 mM in the presence of 30-mu-M 4-AP restored the presynaptic inhibition caused by all effective concentrations of NPY and baclofen. By contrast, inhibition caused by 2-CA was not restored by lowering Ca2+, except at concentrations of 2-CA greater than 10-mu-M. 5 The results are consistent with the hypothesis that presynaptic NPY Y2 and GABA(B) receptors both inhibit transmitter release by the inhibition of voltage-dependent Ca2+ influx, but that the A1 adenosine receptor may activate a different presynaptic mechanism.