Release of endogenous aspartate from rat cerebellum slices and synaptosomes: inhibition mediated by a 5-HT2 receptor and by a 5-HT1 receptor of a possibly novel subtype.
The effects of 5-hydroxytryptamine (5-HT) and of a number of 5-HT receptor agonists and antagonists on the release of endogenous aspartate were investigated in rat cerebellum slices and synaptosomes depolarized with high K+. The release of endogenous aspartate evoked from slices by 35 mmol/l KCl and from synaptosomes by 15 mmol/l KCl was strongly (about 90%) calcium-dependent. In slices the release of aspartate was inhibited by exogenous 5-HT (0.1-100 nmol/l) in a concentration-dependent manner. The indoleamine was very potent, producing 30% inhibition at 0.1 nmol/l. The effect of 10 nmol/l 5-HT was partly but maximally counteracted by ketanserin (300-1000 nmol/l), a 5-HT2 receptor antagonist, but fully blocked by 300 nmol/l of the mixed 5-HT1/5-HT2 receptor antagonist methiothepin. The 5-HT1A receptor agonist 5-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) and the 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) inhibited the K(+)-evoked release of endogenous aspartate in a concentration-dependent manner. The effect of 8-OH-DPAT was antagonized by methiothepin, but not by ketanserin which fully antagonized the inhibition produced by DOI. In cerebellar synaptosomes the release of endogenous aspartate evoked by 15 mmol/l K+ was inhibited by exogenous 5-HT and by 8-OH-DPAT, but not by DOI. Methiothepin (100-300 nmol/l) antagonized the inhibitory effects of 100 nmol/l 5-HT or 8-OH-DPAT. However, 1000 nmol/l of various 5-HT receptor antagonists [ketanserin, methysergide, (--)-propranolol, spiperone or ICS 205-930] did not counteract the effect of 100 nmol/l 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)
Maura
G
G
Istituto di Farmacologia e Farmacognosia, Università degli Studi di Genova, Italy.
Barzizza
A
A
Folghera
S
S
Raiteri
M
M
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D002118:Calcium / Q000502:physiology; D002531:Cerebellum / Q000033:anatomy & histology / Q000378:metabolism*; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D011188:Potassium / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000145:classification / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013574:Synaptosomes / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D000662:Amphetamines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D001224:Aspartic Acid; D012701:Serotonin; D008719:Methiothepin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D011188:Potassium; D002118:Calcium