The ionic basis of inhibitory presynaptic modulation and substance B.
We have investigated the possibility that, regardless of the involvement of a second messenger system, the ultimate effect of presynaptic, receptor-activated inhibitory modulation is the opening of a K channel. This possibility was explored utilizing rat cortical synaptosomes that were prelabeled with either 86Rb or [3H]acetylcholine, depolarizing with either K+ or veratridine, and measuring either efflux of 86Rb or release of [3H]acetylcholine in the presence or absence of inhibitory presynaptic modulators. The modulating agents used were 2-chloroadenosine, carbamylcholine, clonidine, and morphine. In all instances, these agents promoted an increased efflux of 86Rb, indicating hyperpolarization, and decreased release of acetylcholine. These results support our contention that an increase in K conductance may be responsible for presynaptic inhibition of the release of neurotransmitters. We have also found that substance B, a compound that reverses presynaptic modulation, appears to act by closing K channels.
Cooper
J R
JR
Department of Pharmacology, Yale University, School of Medicine, New Haven, Connecticut 06510.
Zoltay
G
G
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D007477:Ions; D009433:Neural Inhibition; D018377:Neurotransmitter Agents / Q000494:pharmacology / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D012413:Rubidium / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D014701:Veratridine / Q000494:pharmacology
D007477:Ions; D018377:Neurotransmitter Agents; D017981:Receptors, Neurotransmitter; D011189:Potassium Chloride; D014701:Veratridine; D012413:Rubidium; D000109:Acetylcholine