Abstract：
:The regulation of cellular responsiveness to dopamine via the D2 dopamine receptor was investigated in mouse fibroblast Ltk-cells stably expressing the rat D2-short receptor [Nature (Lond.) 336:783-787 (1988)]. Dopamine inhibited forskolin-stimulated cAMP levels in these cells (half-maximal inhibition at 3.9 +/- 1.1 nM), and the inhibition by dopamine was blocked by D2 antagonists and was pertussis toxin sensitive. Treatment of these cells with the D2 agonist quinpirole (1 microM) resulted in desensitization of dopaminergic inhibition of forskolin-stimulated cAMP accumulation, with a approximately 4-fold decrease in the potency of dopamine after 1 hr of treatment. No significant changes in total cellular D2 receptor concentrations were observed, even after prolonged agonist treatment. At longer time points, basal and forskolin-stimulated cellular cAMP levels were increased in treated cells. The effect of D2 agonist treatment on membrane adenylyl cyclase (EC 4.6.1.1) activity was examined. Basal and forskolin- and prostaglandin E1-stimulated adenylyl cyclase activities were increased by quinpirole treatment for 24 hr. This sensitization of adenylyl cyclase was blocked by the presence of a D2 antagonist. Pertussis toxin pretreatment blocked the sensitization of adenylyl cyclase by quinpirole, although pertussis toxin also caused increased adenylyl cyclase activity on its own. Sensitization was not dependent upon dopaminergic inhibition of intracellular cAMP levels, because quinpirole treatment in the presence of membrane-permeable cAMP analogs or 3-isobutyl-1-methylxanthine (an inhibitor of cAMP phosphodiesterase) resulted in greater sensitization of adenylyl cyclase activity than quinpirole treatment alone. These results suggest that, in this model system, responsiveness to dopamine via the D2 receptor is regulated by both desensitization of receptor function and sensitization of the stimulatory adenylyl cyclase pathway.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Bates MD,Senogles SE,Bunzow JR,Liggett SB,Civelli O,Caron MGsubject
Has Abstractpub_date
1991-01-01 00:00:00pages
55-63issue
1eissn
0026-895Xissn
1521-0111journal_volume
39pub_type
杂志文章abstract：:We describe the nucleic acid sequence encoding a human 5-hydroxytryptamine1D (5-HT1D) serotonin receptor and some of the functional characteristics of the gene product. The receptor gene was isolated by hybridization to a probe based on a canine thyroid cDNA (called RDC4) previously isolated by others and believed to ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-08-01 00:00:00
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journal_title：Molecular pharmacology
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-11-01 00:00:00
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pub_type： 杂志文章
doi：10.1124/mol.106.026054
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doi：
更新日期：1992-09-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.55.2.364
更新日期：1999-02-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.51.6.944
更新日期：1997-06-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-07-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-01-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1982-11-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-10-01 00:00:00
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pub_type： 评论,杂志文章
doi：10.1124/mol.105.011429
更新日期：2005-04-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-10-01 00:00:00
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pub_type： 杂志文章
doi：10.1124/mol.62.6.1515
更新日期：2002-12-01 00:00:00
abstract：:N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces Parkinson-like symptoms in humans, nonhuman primates, and mice. Several studies suggest that MPTP is metabolized by monoamine oxidase (MAO) type B to yield N-methyl-4-phenyl-pyridinium (MPP+), which is responsible for the neurotoxic effects of the drug. In th...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-03-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1998-05-01 00:00:00
abstract：:Cytochrome P450 (P450) enzymes are responsible for metabolizing drugs. Expression of P450s can directly affect drug metabolism, resulting in various outcomes in therapeutic efficacy and adverse effects. Several nuclear receptors are transcription factors that can regulate expression of P450s at both basal and drug-ind...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.118.112235
更新日期：2018-07-01 00:00:00
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pub_type： 杂志文章
doi：10.1124/mol.59.1.104
更新日期：2001-01-01 00:00:00
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pub_type： 杂志文章
doi：10.1124/mol.112.084616
更新日期：2013-06-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.52.3.473
更新日期：1997-09-01 00:00:00
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pub_type： 杂志文章
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-06-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1994-09-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1992-07-01 00:00:00
abstract：:Corticotropin-releasing factor (CRF) receptors encoded by two distinct genes have recently been identified and termed CRF1 and CRF2. CRF and the non-mammalian-related peptide sauvagine bind to and activate CRF1 receptors with high affinity and equal potency. Although CRF is significantly weaker at the CRF2 receptor, s...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-09-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1983-05-01 00:00:00
abstract：:The selective inactivation by 17 beta-substituted steroids of rabbit and rat liver cytochromes P-450 involved in the 21-hydroxylation of progesterone has been investigated. Five derivatives each of pregnenolone and progesterone were prepared, in which the methylketo substituent of the 17 beta-position was replaced by ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1989-01-01 00:00:00
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pub_type： 杂志文章
doi：10.1124/mol.62.3.638
更新日期：2002-09-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1988-05-01 00:00:00
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journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.111.076208
更新日期：2012-03-01 00:00:00
