Dopaminergic inhibition of catecholamine secretion from chromaffin cells: evidence that inhibition is mediated by D4 and D5 dopamine receptors.
Previous studies have suggested that activation of D2-like dopamine receptors inhibits catecholamine secretion from adrenal chromaffin cells. The purpose of this study was to determine whether the activation of D1-like receptors on chromaffin cells affects either catecholamine release from the cells or the inhibition of secretion by D2-like dopamine receptors. Both D1- and D2-selective agonists inhibited secretion elicited by dimethylphenylpiperazinium (DMPP), veratridine, and high K+ levels. The D1-selective agonists 6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5- tetrahydro-1H-3-benzazepine (CI-APB) and SKF-38393 inhibited DMPP-stimulated catecholamine secretion in a concentration-dependent manner; 50% inhibition was obtained with approximately 10 microM CI-APB and approximately 100 microM SKF-38393. Of the D2-selective agonists, bromocriptine was a more potent inhibitor of DMPP-stimulated catecholamine release than was quinpirole. The inhibition of secretion caused by CI-APB or SKF-38393 was additive with the inhibition caused by bromocriptine. Pertussis toxin treatment (50 ng/ml, 18 h) attenuated the inhibitory effect of D2-selective, but not D1-selective, dopamine agonists. In addition, forskolin-stimulated adenylyl cyclase activity was inhibited by D2-selective, but not D1-selective, agonists. Neither D1- nor D2-selective agonists stimulated adenylyl cyclase activity in the cells, although cyclase activity was stimulated by forskolin, carbachol, and vasoactive intestinal peptide. DMPP-stimulated Ca2+ uptake was inhibited by both D1- and D2-selective dopamine agonists. PCR analysis was used to determine which of the dopamine receptor subtypes within the D1-like and D2-like subfamilies was responsible for the observed inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
Dahmer
M K
MK
Department of Biochemistry, College of Medicine, University of Tennessee, Memphis 38163, USA.
Senogles
S E
SE
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism; D000313:Adrenal Medulla / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001552:Benzazepines / Q000494:pharmacology; D001971:Bromocriptine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D003864:Depression, Chemical; D004246:Dimethylphenylpiperazinium Iodide / Q000037:antagonists & inhibitors; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D008969:Molecular Sequence Data; D037342:Pertussis Toxin; D016133:Polymerase Chain Reaction; D011188:Potassium / Q000037:antagonists & inhibitors; D011954:Receptors, Dopamine / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000502:physiology; D050638:Receptors, Dopamine D4; D050641:Receptors, Dopamine D5; D015290:Second Messenger Systems / Q000187:drug effects; D014701:Veratridine / Q000037:antagonists & inhibitors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D001552:Benzazepines; D002395:Catecholamines; D018491:Dopamine Agonists; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D010566:Virulence Factors, Bordetella; D050638:Receptors, Dopamine D4; D050641:Receptors, Dopamine D5; D005576:Colforsin; D001971:Bromocriptine; D004246:Dimethylphenylpiperazinium Iodide; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D014701:Veratridine; C071262:SK&F 82958; D000242:Cyclic AMP; D037342:Pertussis Toxin; D000262:Adenylyl Cyclases; D011188:Potassium; D002118:Calcium; D004298:Dopamine