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Abstract

Differential pharmacology and function of two 5-HT1 receptors modulating transmitter release in rat cerebellum.

M Raiteri, G Maura, G Bonanno and A Pittaluga
Journal of Pharmacology and Experimental Therapeutics May 1986, 237 (2) 644-648;
M Raiteri
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G Maura
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G Bonanno
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A Pittaluga
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Abstract

The release of endogenous glutamate (GLU) elicited by depolarization of rat cerebellum synaptosomes was inhibited potently (pEC30 = 9.77) by 5-hydroxytryptamine (5-HT). The 5-HT action was antagonized by methiothepin (pA2 = 10.37); ketanserin, methysergide, cinanserin and spiperone were ineffective. Exogenous 5-HT also inhibited the release of [3H]-5-HT from cerebellar synaptosomes (pEC30 = 8.73). Methiothepin, but not ketanserin, methysergide, cinanserin or spiperone counteracted the inhibition (pA2 = 9.28). The receptors involved (presynaptic 5-HT heteroreceptors and autoreceptors) were activated by the 5-HT1 agonist RU 24969 (5-methoxy-3-[1,2,3,6-tetrahydropyridin-4-yl]-1H-indole) which showed comparable activity at the two receptor systems. (-)-Propranolol, used as a 5-HT1 antagonist, shifted to the right (pA2 = 8.05) the dose-response curve of 5-HT at the autoreceptors, but was ineffective at the receptors regulating GLU release. On the contrary, the 5-HT1A agonist 8-hydroxy-2-di-N-propylamino)tetralin activated the presynaptic heteroreceptors (pEC30 = 7.98), but was ineffective as a 5-HT autoreceptor agonist. The results allow the following major conclusions: 5-HT receptors are located on GLU terminals in rat cerebellum where they may modulate in an inhibitory way the release of GLU; 5-HT autoreceptors possibly involved in a negative feedback regulation of 5-HT release are present on cerebellar 5-HT nerve endings; 5-HT autoreceptors and heteroreceptors can be pharmacologically differentiated and appear to represent subtypes of the 5-HT1 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

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Journal of Pharmacology and Experimental Therapeutics
Vol. 237, Issue 2
1 May 1986
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Abstract

Differential pharmacology and function of two 5-HT1 receptors modulating transmitter release in rat cerebellum.

M Raiteri, G Maura, G Bonanno and A Pittaluga
Journal of Pharmacology and Experimental Therapeutics May 1, 1986, 237 (2) 644-648;

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Abstract

Differential pharmacology and function of two 5-HT1 receptors modulating transmitter release in rat cerebellum.

M Raiteri, G Maura, G Bonanno and A Pittaluga
Journal of Pharmacology and Experimental Therapeutics May 1, 1986, 237 (2) 644-648;
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