A study of myocardial muscarinic receptors in streptozotocin-induced diabetic rats using iodine-123 N-methyl-4-iododexetimide

In previous studies we have shown that iodine-123 N-methyl-4-iododexetimide ([I-123]MIDEX) is a suitable single-photon emission tomography radiotracer for the characterisation of myocardial muscarinic acetyl-choline receptors (m-AChR) in the normal state. It has been demonstrated that m-AChR are alt ered as a consequence of diabetes, The aim of the present study was to exam ine myocardial m-AChR density using [I-123]MIDEX in streptozotocin (STZ)-in duced diabetic rats. In vitro binding experiments were conducted on left an d right ventricle and atrium homogenate membranes of 1-week. 5-week and 10- week STZ-induced diabetic and aged-matched normal rats. The m-AChR densitie s (B-max values), as determined by saturation experiments with [I-123]MIDEX , revealed no difference in left and right ventricles or atrium in 1-week a nd 5-week STZ-diabetic rats when compared with normal rats. However, the 10 -week STZ-diabetic group revealed a 39% (P<0.001) decrease in m-AChR densit y in atrium with no change in left and right ventricles, The equilibrium di ssociation constant (K-d values) was similar in all groups. In vitro bindin g autoradiography revealed a 40% decrease in m-AChR density in atrium in th e same 10-week; diabetic rats. No statistically significant difference was found in 1-week and 5-week diabetic rats compared with normals. Ex vivo aut oradiography showed a 50% decrease in [I-123]MIDEX uptake in atrium in 5-we ek diabetic rats and a 60% decrease in 10-week diabetic rats. These results demonstrate the ability of the single-photon agent [I-123]MIDEX to measure in vitro and ex vivo alterations in myocardial m-AChR density observed in STZ-induced diabetic rats.