4-Aminopyridine and low Ca2+ differentiate presynaptic inhibition mediated by neuropeptide Y, baclofen and 2-chloroadenosine in rat hippocampal CA1 in vitro.
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 microM 4-AP. 4-AP reduced the inhibition mediated by all three substances, 100 microM 4-AP was only slightly more effective than 30 microM. 4. Lowering extracellular Ca2+ from 1.5 to 0.75 mM in the presence of 30 microM 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 microM. 5. The results are consistent with the hypothesis that presynaptic NPY Y2 and GABAB 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.
Klapstein
G J
GJ
Department of Pharmacology, University of Alberta, Edmonton, Canada.
Colmers
W F
WF
D015762:2-Chloroadenosine / Q000494:pharmacology; D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002118:Calcium / Q000172:deficiency*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017476:Receptors, Neuropeptide Y; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism; D011983:Receptors, Purinergic / Q000187:drug effects; D013569:Synapses / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects
D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D017981:Receptors, Neurotransmitter; D011983:Receptors, Purinergic; D015762:2-Chloroadenosine; D015761:4-Aminopyridine; D001418:Baclofen; D002118:Calcium