Abstract:
:The interaction of hormones acting via the mobilization of calcium and stimulation of cAMP levels in cells was examined by determining the effects of carbachol and forskolin on cAMP and cGMP accumulation in mouse parotid gland. Treatment of isolated acini with either carbachol (0.01 to 20 microM) or forskolin (1 microM) alone produced little or no increase in cAMP levels; carbachol, however, augmented the effect of forskolin on cAMP accumulation approximately 3- to 4-fold. The effects of carbachol on forskolin-stimulated cAMP levels were further augmented approximately 10-fold in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (MIX) but not in the presence of "low Km" cGMP-inhibited phosphodiesterase inhibitor milrinone. Augmentation of cAMP levels also occurred in the presence of carbachol plus the beta-adrenergic agonist isoproterenol (0.01 microM). In either the presence or absence of forskolin, carbachol increased cGMP levels independently of the inclusion of MIX and in a fashion parallel to that observed for cAMP accumulation. In the presence of forskolin (1 microM), the concentration of carbachol that produced half-maximal effects on cAMP and cGMP levels was 0.62 and 0.72 microM, respectively. Similar values were obtained in the presence of MIX. Cyclic GMP levels were also enhanced by carbachol plus isoproterenol. Hydroxylamine, as well as dibutyryl-cGMP and 8-bromo-cGMP in combination with forskolin, mimicked the effects of carbachol plus forskolin on cAMP levels. LY83583 (6-anillino-5,8-quinolinedione), an agent that lowers cGMP by inhibiting guanylate cyclase, reduced basal levels of cGMP and also completely prevented the increase in cGMP caused by carbachol plus forskolin. In these experiments, however, the augmentation of forskolin-stimulated cAMP levels by carbachol was reduced by approximately 50%. Additional studies suggest that calcium is also required for carbachol augmentation of forskolin-stimulated cAMP accumulation by effects on the adenylate cyclase complex. Augmentation of cAMP levels by carbachol did not involve effects on cAMP degradation. The results suggest that, when cAMP synthesis is stimulated by forskolin or isoproterenol, the muscarinic agonist carbachol augments cAMP accumulation by mechanisms involving cGMP and calcium in mouse parotid gland.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Watson EL,Singh JC,McPhee C,Beavo J,Jacobson KLsubject
Has Abstractpub_date
1990-10-01 00:00:00pages
547-53issue
4eissn
0026-895Xissn
1521-0111journal_volume
38pub_type
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
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journal_title:Molecular pharmacology
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pub_type: 杂志文章
doi:
更新日期:1984-07-01 00:00:00
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doi:
更新日期:1985-01-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
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journal_title:Molecular pharmacology
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doi:
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doi:
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1985-02-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-08-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
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journal_title:Molecular pharmacology
pub_type: 杂志文章
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