- Email: [email protected]
Different subtypes of alpha2-adrenoceptor mediate inhibition of noradrenaline and 5-hydroxytryptamine release in the rat cortex
Pharmacological
Research, Kd. 26, Supplement 1, 1992
143
SYNERGIC MODULATION OF NEUROTENSIN AND CHOLECYSTOKININ OCTAPEPTIDE ON STRIATAL DOPAMINE RELEASE, AS STUDIED BY MICRODIALYSIS. S. Tanganelli, L. Ferraro, C. Bianchi & L. Beani Institute of Pharmacology, University of Ferrara, Italy. The ability of CCK-83 and NT to counteract the D2-agonists-induced inhibition of neostriatal dopamine outflow, is in line with binding studies showing that these peptides reduce the affinity of D2autoreceptors (1, 2, 3). In view of these findings we have evaluated the existence of a possible synergic interaction between CCK-8S and NT in their ability to modulate dopamine outflow in rat neostriatum. Thus the simultaneous perfusion of CCK-8S (1 nM) with increasing concentrations of NT (0,01-l nM) (by themselves ineffective) dose-dependently counteracted the inhibition of dopamine outflow induced by systemic apomorphine treatment (0,05 mg/Kg S.C.). These results suggest that the concomitant release of low concentrations of the two peptides in the extracellular fluid may regulate D2 receptors function. 1) Fuxe K. et al., 1991, Adv. Neuropsychiatry Psychopharmacol., 1: 51. 2) Tanganelli S. et al., 1991, N.-Schmied. Arch. Pharmacol., 342: 300. 3) Von Euler G. et al., 1990, Brain Res., 53: 253.
DIFFERENT SUBTYPES OF ALPHAz-ADRENOCEROR MEDIATE INHIBITION OF NORADRENALINE AND 5-HYDROXYTRYmAMINE RELEASE IN THE RAT CORTEX
Guido Maura, Gianbattista Bonanno, StefanoThellung & Maurizio Raiteri Istituto di Farmacologia e Farmacognosia Universita degli studi di Genova, Viale Cembrano 4, I-16148 Genova, Italy Binding and functional studies strongly suggest an heterogeneity of a2adrenoceptors. In this work a number of a-adrenoceptor antagonists were tested against the noradrenaline inhibition of the depolarisation-evoked 3Hnoradrenaline or 3H-5hydroxytryptamine release from super-fusedrat cerebral cortex synaptosomes and slices. Idazoxan and ORG 20769 were almost equipotent at the autoreceptor (pKB values: 8.45 and 8.42, respectively) and at the heteroreceptor (pKB values: 8.16 and 8.15, respectively). The compound ORG 20350 (pKB value at the autoreceptor: 7.30) was ineffective at the heteroreceptor. In the electrically stimulated cerebral cortex slices ORG 20350 was a competitive antagonist at the a2-heteroreceptor (pA2 value: 7.25 against clonidine). Prazosin (1 pM) and AR-C 239 (1 pM) were ineffective at the autoor heteroreceptor. The results support the conclusion that functional
Research, Kd. 26, Supplement 1, 1992
143
SYNERGIC MODULATION OF NEUROTENSIN AND CHOLECYSTOKININ OCTAPEPTIDE ON STRIATAL DOPAMINE RELEASE, AS STUDIED BY MICRODIALYSIS. S. Tanganelli, L. Ferraro, C. Bianchi & L. Beani Institute of Pharmacology, University of Ferrara, Italy. The ability of CCK-83 and NT to counteract the D2-agonists-induced inhibition of neostriatal dopamine outflow, is in line with binding studies showing that these peptides reduce the affinity of D2autoreceptors (1, 2, 3). In view of these findings we have evaluated the existence of a possible synergic interaction between CCK-8S and NT in their ability to modulate dopamine outflow in rat neostriatum. Thus the simultaneous perfusion of CCK-8S (1 nM) with increasing concentrations of NT (0,01-l nM) (by themselves ineffective) dose-dependently counteracted the inhibition of dopamine outflow induced by systemic apomorphine treatment (0,05 mg/Kg S.C.). These results suggest that the concomitant release of low concentrations of the two peptides in the extracellular fluid may regulate D2 receptors function. 1) Fuxe K. et al., 1991, Adv. Neuropsychiatry Psychopharmacol., 1: 51. 2) Tanganelli S. et al., 1991, N.-Schmied. Arch. Pharmacol., 342: 300. 3) Von Euler G. et al., 1990, Brain Res., 53: 253.
DIFFERENT SUBTYPES OF ALPHAz-ADRENOCEROR MEDIATE INHIBITION OF NORADRENALINE AND 5-HYDROXYTRYmAMINE RELEASE IN THE RAT CORTEX
Guido Maura, Gianbattista Bonanno, StefanoThellung & Maurizio Raiteri Istituto di Farmacologia e Farmacognosia Universita degli studi di Genova, Viale Cembrano 4, I-16148 Genova, Italy Binding and functional studies strongly suggest an heterogeneity of a2adrenoceptors. In this work a number of a-adrenoceptor antagonists were tested against the noradrenaline inhibition of the depolarisation-evoked 3Hnoradrenaline or 3H-5hydroxytryptamine release from super-fusedrat cerebral cortex synaptosomes and slices. Idazoxan and ORG 20769 were almost equipotent at the autoreceptor (pKB values: 8.45 and 8.42, respectively) and at the heteroreceptor (pKB values: 8.16 and 8.15, respectively). The compound ORG 20350 (pKB value at the autoreceptor: 7.30) was ineffective at the heteroreceptor. In the electrically stimulated cerebral cortex slices ORG 20350 was a competitive antagonist at the a2-heteroreceptor (pA2 value: 7.25 against clonidine). Prazosin (1 pM) and AR-C 239 (1 pM) were ineffective at the autoor heteroreceptor. The results support the conclusion that functional