Abstract:
:Cardiac alpha-adrenergic receptors mediate cellular responses to norepinephrine through an undefined series of molecular events. We examined the possibility that phosphoinositide hydrolysis was stimulated through alpha-adrenergic receptors in cardiomyocytes purified from adult rat ventricle. Phosphoinositide stores were labeled with [3H]inositol, and [3H]inositol phosphate formation was assessed after the addition of lithium chloride and norepinephrine. Norepinephrine increased the accumulation of [3H]inositol phosphate by approximately 5-fold, giving a maximal response at approximately 30 microM and a half-maximal response at approximately 1 microM. There was a significant increase in [3H]inositol phosphate formation in response to norepinephrine at 5 minutes, and the response was linear over 40 minutes. Norepinephrine-stimulated [3H]inositol phosphate formation was not blocked by propranolol (1 microM) or yohimbine (0.1 microM) but was completely antagonized by the alpha 1-selective antagonist prazosin (0.1 microM). Muscarinic cholinergic receptor activation by carbachol also stimulated [3H]inositol phosphate formation in rat ventricular myocytes. The maximal effect of carbachol (approximately 2-fold) was always less than that of norepinephrine. The combined effects of norepinephrine and carbachol were additive, suggesting that the two hormones do not share a common rate-limiting step. Removal of extracellular calcium and addition of ethylene glycol bis(beta-amino ether)-N,N'-tetraacetic acid, attenuated, but did not abolish, norepinephrine- or carbachol-stimulated [3H]inositol phosphate formation. Neither the calcium ionophore A23187 nor the calcium channel blockers verapamil and nifedipine had any effect on basal or hormone-stimulated [3H]inositol phosphate formation. We suggest that some of the physiological and metabolic effects of adrenergic and cholinergic stimulation on the rat myocardium are secondary to receptor-mediated hydrolysis of phosphoinositides.
journal_name
Circ Resjournal_title
Circulation researchauthors
Brown JH,Buxton IL,Brunton LLdoi
10.1161/01.res.57.4.532subject
Has Abstractpub_date
1985-10-01 00:00:00pages
532-7issue
4eissn
0009-7330issn
1524-4571journal_volume
57pub_type
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章,评审
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更新日期:2019-01-04 00:00:00
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更新日期:2016-08-19 00:00:00
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pub_type: 杂志文章
doi:10.1161/01.res.62.1.81
更新日期:1988-01-01 00:00:00
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更新日期:1999-06-25 00:00:00
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更新日期:2016-05-13 00:00:00
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更新日期:2009-01-30 00:00:00
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更新日期:1998-06-29 00:00:00
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更新日期:1975-06-01 00:00:00
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更新日期:1992-06-01 00:00:00
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更新日期:1977-04-01 00:00:00
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pub_type: 杂志文章
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更新日期:2005-09-16 00:00:00