Presynaptic displacement of serotonin by alpha-methyl-5-hydroxytryptamine in the nucleus tractus solitarius of the rat.
Rat brain slices containing the nucleus tractus solitarius loaded with [3H]5-hydroxytryptamine ([3H]5-HT) for superfusion were stimulated at (3 Hz, 25 mA, 1 min) resulting in fractional release ratios S2/S1 of 0.89 for [3H]5-HT in the presence of the serotonin uptake inhibitor 1.0 microM 6-nitroquipazine (6-NQ). alpha-Methylserotonin (alpha-Me-5-HT; 1.0 microM), a non-selective 5-HT1 and 5-HT2 receptor agonist, significantly reduced the S2/S1 ratio of [3H]5-HT without affecting the basal release ratios B2/B1 1.00 +/- 0.04. Without 6-NQ in the perfusion medium 1.0 microM alpha-Me-5-HT sharply increased the basal release B2/B1 to 2.21 (P < 0.01). In low Ca2+ medium the S2/S1 ratio was reduced to 0.06 and alpha-Me-5-HT promoted a B2/B1 release of 2.17 (P < 0.01). The 5-HT3 antagonist LY-278,584 did not block alpha-Me-5-HT induced basal release of [3H]5-HT. Both pindolol and LY-53,857 blocked the autoinhibitory effects of alpha-Me-5-HT, but only LY-53,857 and 6-NQ blocked the basal release induced by alpha-Me-5-HT. These results suggest that alpha-Me-5-HT reduces neurotransmitter release through the serotonin autoreceptor and displaces serotonin through a non-exocytotic release mechanism.
Helfman
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Department of Physiology, Wayne State University, School of Medicine, Detroit, MI 48201, USA.
Anderson
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GF
Barraco
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RA
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000378:metabolism / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism*
D002712:Chlorides; D011188:Potassium; D017661:Receptors, Presynaptic; D012701:Serotonin; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D012964:Sodium; C042390:alpha-methylserotonin