Increased muscarinic responsiveness and decreased muscarinic receptor content in ileal smooth muscle in diabetes.
Longitudinal muscles from the ileum of rats rendered diabetic for 10 to 12 weeks by injection of streptozotocin (STZ) developed greater contractile force in response to muscarinic agonists, (acetylcholine, carbamylcholine and bethanechol) than muscles from age-matched control rats. There was no change, however, in the sensitivity of longitudinal smooth muscles to muscarinic agonists as reflected by the EC50 values for stimulation of muscle contraction. This increased responsiveness of the muscles was accompanied by a 32% reduction in the density of muscarinic receptors (381 +/- 93 vs. 560 +/- 74 fmol/mg of membrane protein) in muscles from STZ-diabetic rats. There was no change in agonist or antagonist binding affinities in muscles from diabetic rats, and there was no alteration in the distribution of receptors between the states characterized by high and low affinity agonist binding. There was also no change in acetylcholinesterase activity in muscle membranes isolated from STZ-diabetic rats. The origin of the increased responsiveness of ileal smooth muscles in this model of diabetes is not clear, but may involve changes in the muscarinic signal transduction pathway beyond the receptor level, or in the contractile apparatus itself.
Carrier
G O
GO
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta.
Aronstam
R S
RS
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007082:Ileum; D007275:Injections, Intravenous; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D019832:N-Methylscopolamine; D010276:Parasympatholytics / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D012602:Scopolamine Derivatives / Q000378:metabolism / Q000494:pharmacology*
D001786:Blood Glucose; D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D012602:Scopolamine Derivatives; D000110:Acetylcholinesterase; D019832:N-Methylscopolamine