DIABETES-INDUCED ALTERATIONS IN THE PROPERTIES OF MUSCARINIC CHOLINERGIC RECEPTORS IN RAT VAS-DEFERENS

Muscarinic cholinergic receptors were identified and characterized by radioligand receptor binding assay using [H-3]quinuclidinyl benzilate (QNB) in rat vas deferens membrane particulates of three experimental groups: 1) 8-week diabetic, 2) 8-week diabetic insulin-treated and 3) age-matched control. Diabetes was induced by the intravenous injection of 65 mg./kg. streptozotocin (STZ). The density of muscarinic recepto rs (B-max values), as determined by saturation experiments with [H-3]Q NB, was demonstrated to be higher in the vas deferens of diabetic rats than in the vas deferens of control and diabetic insulin-treated rats . The equilibrium dissociation constants (K-D values), however; were s imilar in all three groups. Muscarinic cholinergic antagonists compete d with [H-3]QNB binding sites in the vas deferens membrane particulate s with the following rank order of K-i values: atropine < methoctramin e less than or equal to 4-DAMP < AF-DX 116 < HHSiD < pirenzepine = pfH HSiD. The pharmacological profile of muscarinic receptors was similar in all three groups. Additional pharmacological studies showed a simil ar rank order of K-i values for vas deferens, bladder dome and heart, but this rank order was significantly different in cerebral cortex and prostate. This is consistent with the predominance of the M(2) muscar inic cholinergic receptor subtype in the rat vas deferens. It is concl uded that STZ-induced diabetes causes an upregulation of muscarinic ch olinergic receptor density in the rat vas deferens that can be prevent ed by the administration of insulin.