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| Content Provider | PubMed Central |
|---|---|
| Author | Cao, Guihua Gardner, Alice Westfall, Thomas C. |
| Abstract | In rat pheochromocytoma (PC-12) cells the dopamine D2 receptor agonists apomorphine (APO) and n-propylnorapomorphine (NPA) produced a concentration dependent inhibition of K+-evoked neuropeptide Y release (NPY-ir). The effect of APO was blocked by the dopamine D2-receptor antagonist, eticlopride, but not the D1/D3 or the D4/D2 antagonists, SCH23390 or clozapine, respectively. The D1/D5 receptor agonist, SKF38393 or the D3 agonists PD128907 and 7-OH DPAT had no effect. Selective N and L-type voltage gated Ca2+ channel blockers, ω-Conotoxin GVIa (Ctx-GVIa) and nifedipine, respectively, produced a concentration dependent inhibition of NPY-ir release but were not additive with APO. The Ca2+/calmodulin-dependent protein kinase (CaM kinase) II inhibitor KN-62 produced a concentration-dependent inhibition of NPY-ir release but the combination of KN-62 and APO produced no further inhibition. PMA-mediated protein kinase C stimulation significantly increased both basal and K+-evoked release of NPY-ir, and in the presence of PMA APO had no inhibitory effect. The PKC antagonist, chelerythrine, inhibited K+-evoked NPY-ir release but was not additive with APO. Neither forskolin-mediated adenylate cyclase activation and the active cAMP analog Sp-cAMPS, nor the adenylate cyclase inhibitor SQ 22536, and the competitive inhibitor of cAMP-dependent protein kinases Rp-cAMPS, had any significant effect on K+-evoked NPY-ir release. This suggests the inhibitory effect of APO on K+-evoked release of NPY-ir from PC 12 cells is most likely mediated through activation of dopamine D2 receptors leading to direct inhibition of N and L-type voltage gated Ca2+ channels, or indirect inhibition of PKC, both of which would reduce [Ca2+]i and inactivate CaM kinase. |
| Related Links | http://dx.doi.org/10.1016/j.bcp.2007.01.003 |
| Starting Page | 1446 |
| File Format | |
| ISSN | 18732968 |
| e-ISSN | 18732968 |
| Journal | Biochemical pharmacology |
| Issue Number | 9 |
| Volume Number | 73 |
| Language | English |
| Publisher Date | 2007-05-01 |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biochemistry Pharmacology |
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