7-OH-DPAT-induced inhibition of norepinephrine release in PC12 cells.
The purpose of this study was to investigate mechanisms of suppression of norepinephrine release by 7-OH-DPAT, a dopamine D(2)/D(3) receptor agonist, in PC12 cells pretreated with nerve growth factor (NGF). 7-OH-DPAT caused inhibition of basal and K(+)-evoked norepinephrine release, which could be blocked by pretreatment with raclopride, a D(2)/D(3) receptor antagonist. Moreover, dopamine D(2) and D(3 )receptors were identified by immunocytochemistry. Expression of D(2), D(3), and D(4) mRNAs and their proteins were detected using RT-PCR and immunoblotting. Furthermore, 7-OH-DPAT produced no change in cGMP levels; however, 7-OH-DPAT inhibited forskolin-stimulated cAMP accumulation that was antagonized by pretreatment with raclopride. In addition, 7-OH-DPAT inhibited carbachol-induced Ca(2+) transient, conversely, 7-OH-DPAT had no effect on 4-aminopyridine-induced Ca(2+) transient. Taken together, suppression of cAMP accumulation and calcium mobilization by 7-OH-DPAT is involved in the inhibition of norepinephrine release through activation of dopamine D(2)/D(3) receptors.
Chu
Eugenia
E
University of Georgia, Athens, GA, USA.
Chu
Jane
J
Socci
Robin R
RR
Chu
Teh-Ching
TC
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D015151:Immunoblotting; D007120:Immunochemistry; D020932:Nerve Growth Factor / Q000494:pharmacology; D009638:Norepinephrine / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016716:PC12 Cells / Q000187:drug effects* / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D050637:Receptors, Dopamine D3; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013764:Tetrahydronaphthalenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D065127:Dopamine D2 Receptor Antagonists; C493595:Drd3 protein, rat; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; D005576:Colforsin; D020891:Raclopride; D011189:Potassium Chloride; D002217:Carbachol; D020932:Nerve Growth Factor; D000242:Cyclic AMP; C031349:7-hydroxy-2-N,N-dipropylaminotetralin; D002118:Calcium; D009638:Norepinephrine