[Molecular causes of changes in sensitivity of adenylyl cyclase signaling system to biogenic amines in the heart muscle during experimental streptozotocin diabetes].
Changes in hormonal sensitivity of the adenylyl cyclase signaling system (ACS) and their possible molecular causes in the heart muscle of rats with experimental streptozotocin diabetes (type I diabetes) are investigated. An increase in stimulating effects of noradrenaline and isoproterenol on adenylyl cyclase (AC) activity have been shown. In the case of noradrenaline, this increase is due to suppression of Gi-protein function and Gi-coupled inhibitory AC signaling pathway. Meanwhile, in diabetic rats the influence of C-terminal peptide 346-355 of alphai2-subunit on hormonal activation of AC and GTP-binding is diminished. In the case of isoproterenol, along with its stimulating effect, at micromolar concentrations this hormone exerts inhibitory action, realized, presu- mably, through beta3-adrenergic receptors. Effect of isoproterenol on AC and GTP-binding in the heart of diabetic animals is modified by peptide 385-394 alphas, blocking Gs-coupled signaling pathways, and by peptide 346-355 alphai2, blocking transduction of inhibitory signals. In addition, a decrease in serotonin stimulating effect on components of ACS in diabetic animals was shown. The data obtained provide evidence for changes in ACS function in diabetes, which can be detected mainly at the G-protein level. The proposed peptide strategy is a new and perspective approach for studying molecular causes of functional violations in hormonal signaling systems arising at endocrine pathology.
Shpakov
A O
AO
Kuznetsova
L A
LA
Plesneva
S A
SA
Gur'ianov
I A
IA
Pertseva
M N
MN
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006321:Heart / Q000187:drug effects*; D036341:Intercellular Signaling Peptides and Proteins; D007545:Isoproterenol / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000494:pharmacology; D015398:Signal Transduction; D013311:Streptozocin / Q000009:adverse effects
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D036341:Intercellular Signaling Peptides and Proteins; D012701:Serotonin; D013311:Streptozocin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D009638:Norepinephrine