Release of serotonin from nerve endings byl-5-hydroxytryptophan,?-methyl-m-tyramine, and elevated potassium ions

Abstract

The release of [(3)H]5-hydroxytryptamine ([(3)H]5-HT) byL-5-hydroxytryptophan (L-5-HTP),α-methyl-m-tyramine (α-MMTA), and elevated levels of K(+) was studied using crude synaptosomal preparations (P2) isolated from the telencephalon of the rat and pigeon. Studies were conducted in vitro in the presence of either 2×10(-5) M tranylcypromine, which inhibited the MAO activity of both the extrasynaptosomal mitochondria and the mitochondria contained within the nerve endings (intrasynaptosomal mitochondria), or 2×10(-5) M nialamide, which inhibited the MAO activity of the extrasynaptosomal mitochondria under the experimental conditions used. In the P2 fraction isolated from the rat, either 55 mM K(+), 0.10 mML-5-HTP, or 0.03 mMα-MMTA significantly increased the release of [(3)H]5-HT above control levels, regardless of which MAO inhibitor was present in the medium. In the presence of tranylcypromine, this increased release by 55 mM K(+) or 0.10 mML-5-HTP was partially suppressed if Ca(2+) was omitted from the medium. In the presence of nialamide, the release by 55 mM K(+) was completely prevented if Ca(2+) was omitted; the release byL-5-HTP was only partially affected. The release of [(3)H]5-HT byα-MMTA did not appear to be markedly affected by removal of Ca(2+), regardless of which MAO inhibitor was present. Very similar data were obtained in the presence of nialamide using the P2 fraction isolated from the telencephalon of the pigeon, with the exception that 0.10 mML-5-HTP caused an increase in the release of [(3)H]5-HIAA (which was not calcium-dependent) instead of [(3)H]5-HT. The data are discussed in.