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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Cartmell, J. Schaffhauser, H. Mutel, V. Wichmann, J. |
| Description | Author Affiliation: Cartmell J ( Pharma Division Pre-clinical Research, F. Hoffmann-La Roche Ltd., Basel, Switzerland.) |
| Abstract | 1. The effects of selective agonists at group I, II and III metabotropic glutamate receptors (mGluRs) on adenosine A2 receptor-mediated cyclic AMP formation were compared in cross-chopped slices of adult and neonatal (8 days old) rat striatum, in the presence of 1 u ml(-1) adenosine deaminase. 2. The group II selective agonist, (2S,1R,2R,3R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV), elicited a potentiation of 5'-N-ethylcarboxamidoadenosine (NECA)-stimulated cyclic AMP production with similar potencies in adult (EC50 value 122 +/- 35 nM) and neonatal (EC50 value 285 +/-6 nM) brain. In contrast, the group I selective agonist (S)-dihydroxyphenylglycine ((S)-DHPG) augmented the NECA cyclic AMP response in neonatal striatum (EC50 value 9 +/- 1 microM), but at a concentration of 100 microM, (S)-DHPG failed to affect the NECA response in adult striatal slices. 3. The potentiation evoked by (S)-DHPG was specific for group I mGluRs as (2S,3S,4S,)-2-methyl-2-(carboxycyclopropyl)glycine (MCCG), a group II antagonist, was ineffective on the (S)-DHPG (100 microM) response at a concentration (500 microM) which reversed a similar augmentation elicited by DCG-IV (300 nM). Furthermore, a protein kinase C inhibitor (Ro 31-8220, 10 microM) markedly reversed the effect of (S)-DHPG without affecting the response to DCG-IV. 4. The mGluR agonist (2S,3S,4S,)-alpha-(carboxycyclopropyl)glycine (L-CCG-I), elicited a greater potentiation of NECA-stimulated cyclic AMP production in neonatal striatum in comparison with that observed in adult rat brain. Moreover, EC50 values obtained from adult and neonatal striatum were 2 +/-1 microM and 9 +/-1 microM, respectively. These differences in potency might reflect co-activation of both group I and group II mGluRs by L-CCG-I in neonatal striatum. 5. Distinct patterns of mGluR expression in various brain areas might account for previous conflicting data on the nature of the mGluR able to evoke such potentiated responses. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 7 |
| Volume Number | 121 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1997-08-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Corpus Striatum Metabolism Cyclic AMP Biosynthesis Receptors, Glutamate Physiology Adenosine Analogs & Derivatives Pharmacology Adenosine-5'-(N-ethylcarboxamide) Animals Animals, Newborn Glycine In Vitro Techniques Rats, Sprague-Dawley |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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