α-Adrenergic supersensitivity and decreased number of α-adrenoceptors in heart from acute diabetic rats
The inotropic effect of methoxamine, as well as the α-adrenoceptor population, were measured in cardiac tissue from normal and short-term (3 days) diabetic rats. Methoxamine increased the tension of both normal and diabetic ventricles, but in diabetic ones, the dose-response curve to methoxamine was...
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1988
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00084212_v66_n9_p1154_Wald http://hdl.handle.net/20.500.12110/paper_00084212_v66_n9_p1154_Wald |
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paper:paper_00084212_v66_n9_p1154_Wald2023-06-08T14:32:01Z α-Adrenergic supersensitivity and decreased number of α-adrenoceptors in heart from acute diabetic rats 1 (5 isoquinolinesulfonyl) 2 methylpiperazine alpha adrenergic receptor diacylglycerol methoxamine n (2 aminoethyl) 5 isoquinolinesulfonamide phentolamine prazosin propranolol animal cell animal experiment controlled study diabetes mellitus heart ventricle inotropism male nonhuman priority journal rat Animal Diabetes Mellitus, Experimental Dose-Response Relationship, Drug Kinetics Male Methoxamine Myocardial Contraction Myocardium Prazosin Rats Rats, Inbred Strains Receptors, Adrenergic, alpha Support, Non-U.S. Gov't The inotropic effect of methoxamine, as well as the α-adrenoceptor population, were measured in cardiac tissue from normal and short-term (3 days) diabetic rats. Methoxamine increased the tension of both normal and diabetic ventricles, but in diabetic ones, the dose-response curve to methoxamine was shifted to the left and the efficacy of the α-agonist was enhanced. This phenomenon was accompanied by an increase in receptor affinity, while the number of α-adrenoceptor sites decreased. Inhibitors of α1-adrenoceptors blocked, in a competitive manner, the positive inotropic effect of methoxamine in both types of ventricles. Inhibition of phospholipase C blocked the ventricular response to the methoxamine in nondiabetic as well as in diabetic hearts. Synthetic diacylglyceride (DAG) potentiated the inotropic action of the α-agonist in normal ventricles and increased the affinity with a decreased number of α-adrenoceptor sites in normal ventricles, producing values of K(d) of B(max) similar to those of the acute diabetic heart. Inhibitors of protein kinase C partially reduced the supersensitivity to α-agonists in diabetic ventricles and prevented the stimulatory action of DAG upon the positive inotropic effect of methoxamine in normal ventricles. These results suggest that α-adrenergic inotropic stimulation is secondary to receptor-mediated hydrolysis of phosphoinositides, generating some oxidative metabolites (DAG) which, in turn, may be responsible for the inotropic effect. In the acute diabetic state, the supersensitivity to α-agonist could be due to high activity of phospholipase C (with an increase in DAG production) which induces alteration in the membrane α-adrenergic receptors. 1988 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00084212_v66_n9_p1154_Wald http://hdl.handle.net/20.500.12110/paper_00084212_v66_n9_p1154_Wald |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
1 (5 isoquinolinesulfonyl) 2 methylpiperazine alpha adrenergic receptor diacylglycerol methoxamine n (2 aminoethyl) 5 isoquinolinesulfonamide phentolamine prazosin propranolol animal cell animal experiment controlled study diabetes mellitus heart ventricle inotropism male nonhuman priority journal rat Animal Diabetes Mellitus, Experimental Dose-Response Relationship, Drug Kinetics Male Methoxamine Myocardial Contraction Myocardium Prazosin Rats Rats, Inbred Strains Receptors, Adrenergic, alpha Support, Non-U.S. Gov't |
| spellingShingle |
1 (5 isoquinolinesulfonyl) 2 methylpiperazine alpha adrenergic receptor diacylglycerol methoxamine n (2 aminoethyl) 5 isoquinolinesulfonamide phentolamine prazosin propranolol animal cell animal experiment controlled study diabetes mellitus heart ventricle inotropism male nonhuman priority journal rat Animal Diabetes Mellitus, Experimental Dose-Response Relationship, Drug Kinetics Male Methoxamine Myocardial Contraction Myocardium Prazosin Rats Rats, Inbred Strains Receptors, Adrenergic, alpha Support, Non-U.S. Gov't α-Adrenergic supersensitivity and decreased number of α-adrenoceptors in heart from acute diabetic rats |
| topic_facet |
1 (5 isoquinolinesulfonyl) 2 methylpiperazine alpha adrenergic receptor diacylglycerol methoxamine n (2 aminoethyl) 5 isoquinolinesulfonamide phentolamine prazosin propranolol animal cell animal experiment controlled study diabetes mellitus heart ventricle inotropism male nonhuman priority journal rat Animal Diabetes Mellitus, Experimental Dose-Response Relationship, Drug Kinetics Male Methoxamine Myocardial Contraction Myocardium Prazosin Rats Rats, Inbred Strains Receptors, Adrenergic, alpha Support, Non-U.S. Gov't |
| description |
The inotropic effect of methoxamine, as well as the α-adrenoceptor population, were measured in cardiac tissue from normal and short-term (3 days) diabetic rats. Methoxamine increased the tension of both normal and diabetic ventricles, but in diabetic ones, the dose-response curve to methoxamine was shifted to the left and the efficacy of the α-agonist was enhanced. This phenomenon was accompanied by an increase in receptor affinity, while the number of α-adrenoceptor sites decreased. Inhibitors of α1-adrenoceptors blocked, in a competitive manner, the positive inotropic effect of methoxamine in both types of ventricles. Inhibition of phospholipase C blocked the ventricular response to the methoxamine in nondiabetic as well as in diabetic hearts. Synthetic diacylglyceride (DAG) potentiated the inotropic action of the α-agonist in normal ventricles and increased the affinity with a decreased number of α-adrenoceptor sites in normal ventricles, producing values of K(d) of B(max) similar to those of the acute diabetic heart. Inhibitors of protein kinase C partially reduced the supersensitivity to α-agonists in diabetic ventricles and prevented the stimulatory action of DAG upon the positive inotropic effect of methoxamine in normal ventricles. These results suggest that α-adrenergic inotropic stimulation is secondary to receptor-mediated hydrolysis of phosphoinositides, generating some oxidative metabolites (DAG) which, in turn, may be responsible for the inotropic effect. In the acute diabetic state, the supersensitivity to α-agonist could be due to high activity of phospholipase C (with an increase in DAG production) which induces alteration in the membrane α-adrenergic receptors. |
| title |
α-Adrenergic supersensitivity and decreased number of α-adrenoceptors in heart from acute diabetic rats |
| title_short |
α-Adrenergic supersensitivity and decreased number of α-adrenoceptors in heart from acute diabetic rats |
| title_full |
α-Adrenergic supersensitivity and decreased number of α-adrenoceptors in heart from acute diabetic rats |
| title_fullStr |
α-Adrenergic supersensitivity and decreased number of α-adrenoceptors in heart from acute diabetic rats |
| title_full_unstemmed |
α-Adrenergic supersensitivity and decreased number of α-adrenoceptors in heart from acute diabetic rats |
| title_sort |
α-adrenergic supersensitivity and decreased number of α-adrenoceptors in heart from acute diabetic rats |
| publishDate |
1988 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00084212_v66_n9_p1154_Wald http://hdl.handle.net/20.500.12110/paper_00084212_v66_n9_p1154_Wald |
| _version_ |
1768542108985065472 |