Relations between contractile responses and beta-adrenoceptors in gastric fundus of diabetic rats

Contractile responses to norepinephrine (NE), and the population of beta-adrenoceptors, were determined in gastric fundus smooth muscle from rats with diabetes induced by streptozotocin (STZ), and age-matched controls. Relaxation and/or contraction of fundus strips of controls and diabetics were induced by 10(-5)M NE. Responses to NE were mainly relaxation in gastric fundus isolated from controls, and contraction in fundus isolated from diabetics. Contraction was blocked by 10(-8) M prazosin and relaxation was blocked by 10(-6) M propranolol. Relaxation by isoproterenol of contraction induced by 10(-6) M acetylcholine was significantly less in fundus from diabetics than in that from controls. The number of beta-adrenoceptors, measured with [125I] iodocyanopindolol as a ligand, was significantly less in gastric fundus membrane isolated from diabetics than in that from controls, but affinity was no different. The level of plasma catecholamine was higher in diabetics than in controls. Results suggest that depression of gastric fundus relaxation and increase of contraction by NE in diabetics could be due to fewer beta-adrenoceptor binding sites caused by down-regulation by higher catecholamine level in diabetic rats.