Calcitonin gene-related peptide-mediated increase in K(+)-induced [(3)H]-dopamine release from rat caudal striatal slices.
The calcitonin-gene receptor peptide (alphaCGRP) receptor is present in high levels in the caudal striatum of the rat. Previous behavioural experiments have highlighted a possible correlation between alphaCGRP-mediated effects and the dopaminergic system. In this study, we examined the effect of alphaCGRP on K(+)-evoked [(3)H]-dopamine release in a slice preparation of the rat caudal striatum. The unstimulated release of [(3)H]-dopamine was not affected by alphaCGRP. However, alphaCGRP increased the release of [(3)H]-dopamine evoked by K(+) (30 mM) in a concentration-dependent manner. The stimulatory effect of alphaCGRP was blocked by the CGRP1 antagonist hCGRP(8-37) (without effect on its own). The stimulatory effect of 1 microM alphaCGRP was blocked by dizocilpine (MK-801), suggesting that excitatory transmission is involved in mediating the facilitated release. This study suggests that the peptide alphaCGRP, modulates dopamine release in the rat caudal striatum probably indirectly via glutamatergic transmission.
Maneuf
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Pfizer Global Research & Development, Cambridge Laboratories, University of Cambridge Forvie site, Robinson Way, Cambridge CB2 2QB, UK. yannick.maneuf@pfizer.com
McKnight
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D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002421:Caudate Nucleus / Q000378:metabolism*; D004298:Dopamine / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D008916:Miotics / Q000494:pharmacology; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014316:Tritium
D008916:Miotics; D010446:Peptide Fragments; D018015:Receptors, Calcitonin Gene-Related Peptide; D014316:Tritium; C058636:calcitonin gene-related peptide (8-37); D018698:Glutamic Acid; D015740:Calcitonin Gene-Related Peptide; D011188:Potassium; D004298:Dopamine