The contribution of different types of calcium channels to electrically-evoked adenosine release from rat hippocampal slices.
The role of L-, N- and P-type voltage-dependent calcium channels (VDCCs) in the release of adenosine from rat hippocampal slices was investigated by evaluating the effect of the L-channel activator 1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)-phenyl]-3-pyr idi ne carboxylic acid methyl ester (Bay K 8644) and of three calcium channel antagonists: the L-channel antagonist nifedipine, the N-channel blocker omega-conotoxin GVIA (omega-CgTx) and the P-channel blocker omega-agatoxin IVA (omega-Aga-IVA). Adenosine and inosine release, evoked by 5 min electrical stimulation at 10 Hz of hippocampal slices, was assayed by HPLC with ultraviolet absorbance or fluorimetric detection. Nifedipine (100 nM) did not affect adenosine and inosine release evoked by electrical stimulation. Bay K 8644 (100 nM) brought about a statistically significant increase in adenosine evoked release (70%). At a higher concentration (1 microM) Bay K 8644 had no significant effect either on adenosine or inosine release evoked by electrical stimulation. The increase in adenosine release elicited by 100 nM Bay K 8644 was abolished by nifedipine (100 nM). Both omega-CgTx (10 microM) and omega-Aga-IVA (200 nM) caused a statistically significant reduction (77-78%) in evoked release of adenosine. When the previously demonstrated glutamate-dependent component of the release of adenosine was suppressed in the presence of the NMDA and non-NMDA receptor antagonists, D(-)-2-amino-7-phosphonoheptanoic acid (D-AP7. 100 microM) and 6,7-dinitroquinoxaline-2,3-dione (DNQX, 10 microM), the remaining release of adenosine was again significantly reduced by omega-CgTx (10 microM) (60%) and omega-Aga-IVA (200 nM) (73%). These data suggest that, while L-type VDCCs are involved in the regulation of the evoked release of adenosine only when activated by Bay K 8644, both P- and N-channels play a direct role in the calcium entry involved in the coupling process between electrical stimulation and adenosine release.
Latini
S
S
Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
Pedata
F
F
Pepeu
G
G
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D004558:Electric Stimulation; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013111:Spider Venoms / Q000494:pharmacology; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D020866:omega-Conotoxin GVIA; D009543:Nifedipine; D000241:Adenosine