Muscarinic receptor density is reduced in diabetic rat atria, an effect prevented by the aldose reductase inhibitor, Statil.
Binding assays using [3H]quinuclidinyl benzilate (QNB) as a muscarinic receptor ligand were carried out on atrial tissue from 6 control and 11 six-week streptozocin-diabetic rats. Five of the latter had received the aldose reductase inhibitor, Statil (25 mg kg-1 day-1 orally). Dissociation constants for specific (atropine displaceable QNB) binding were not changed either by diabetes or Statil treatment. Muscarinic receptor numbers, as estimated by Bmax values, were, however, significantly depressed in tissues from the untreated diabetic group, compared with tissues from either the controls or the Statil-treated diabetic group. These results may explain the reduced sensitivity to muscarinic agonists previously observed in atria from similarly diabetic rats and indicate the involvement of the sorbitol pathway in the change. Possible mechanisms are discussed.
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010793:Phthalazines / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D011813:Quinuclidinyl Benzilate; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D010793:Phthalazines; D011724:Pyridazines; D011976:Receptors, Muscarinic; C042829:ponalrestat; D011813:Quinuclidinyl Benzilate; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase