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 ([123I]MIDEX) is a suitable single-photon emission tomography radiotracer for the characterisation of myocardial muscarinic acetylcholine receptors (m-AChR) in the normal state. It has been demonstrated that m-AChR are altered as a consequence of diabetes. The aim of the present study was to examine myocardial m-AChR density using [123I]MIDEX in streptozotocin (STZ)-induced diabetic rats. In vitro binding experiments were conducted on left and 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 densities (Bmax values), as determined by saturation experiments with [123I]MIDEX, revealed no difference in left and right ventricles or atrium in 1-week and 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 density in atrium with no change in left and right ventricles. The equilibrium dissociation constant (Kd values) was similar in all groups. In vitro binding autoradiography revealed a 40% decrease in m-AChR density in atrium in the same 10-week diabetic rats. No statistically significant difference was found in 1-week and 5-week diabetic rats compared with normals. Ex vivo autoradiography showed a 50% decrease in [123I]MIDEX uptake in atrium in 5-week diabetic rats and a 60% decrease in 10-week diabetic rats. These results demonstrate the ability of the single-photon agent [123I]MIDEX to measure in vitro and ex vivo alterations in myocardial m-AChR density observed in STZ-induced diabetic rats.
Mardon
K
K
Radiopharmaceutical Division R&D, Australian Nuclear Science and Technology Organisation, Sydney NSW, Australia.
Kassiou
M
M
Katsifis
A
A
Najdovski
L
L
D000818:Animals; D018678:Cholinergic Agents; D003909:Dexetimide / Q000031:analogs & derivatives*; D003921:Diabetes Mellitus, Experimental / Q000000981:diagnostic imaging / Q000378:metabolism*; D006321:Heart / Q000000981:diagnostic imaging*; D007457:Iodine Radioisotopes; D008297:Male; D009206:Myocardium / Q000378:metabolism; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000032:analysis*
D018678:Cholinergic Agents; D007457:Iodine Radioisotopes; C094599:N-methyl-4-iododexetimide; D011976:Receptors, Muscarinic; D003909:Dexetimide