Diabetes-induced changes in the Gi-modulated muscarinic receptor-adenylyl cyclase system in rat myocardium.

• The inhibitory guanine nucleotide binding regulatory protein (Gi)-mediated muscarinic receptor-adenylyl cyclase system was studied in myocardium from adult male Wistar rats with 10 weeks of diabetes induced by a single intravenous injection of streptozotocin (60 mg/kg). Neither the messenger ribonucleic acid level nor the amount of Gi was changed in the streptozotocin diabetic group as compared to the control group. The activity of the adenylyl cyclase stimulated by guanyliminodiphosphate was decreased by 48% in the streptozotocin diabetic group whereas stimulated activities of adenylyl cyclase by sodium fluoride and forskolin remained unchanged. The inhibition of forskolin-stimulated adenylyl cyclase activity by carbachol was more potent in membranes from the streptozotocin diabetic group than that in membranes from the control group. The competition binding curve between (3H)- quinuclidinyl benzilate and carbachol obtained from the streptozotocin diabetic group was shifted to the left as compared to the control group. These results suggest that the myocardium of streptozotocin-induced diabetic rats exhibited an increase in Gi function as demonstrated by the increased inhibition of guanyliminodiphosphate-mediated adenylyl cyclase and the superhigh affinity for carbachol of the muscarinic receptors. As there were signs, similar to those seen in clinical heart failure, in the streptozotocin diabetic group, these results demonstrate that functional alteration of Gi might underlie, at least in part, the cardiac dysfunction that is associated with diabetes.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Nyckelord

Adenylate Cyclase

metabolism

Amino Acid Sequence

Animals

Blotting

Northern

Body Weight

Cell Membrane

Diabetes Mellitus

Experimental

metabolism

Enzyme-Linked Immunosorbent Assay

GTP-Binding Proteins

chemistry

genetics

metabolism

Guanylyl Imidodiphosphate

metabolism

Male

Molecular Sequence Data

Myocardium

metabolism

Peptide Fragments

chemistry

RNA

Messenger

metabolism

Rats

Rats

Wistar

Receptors

Muscarinic

metabolism

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)