title: Cardiac beta-adrenergic receptors in diabetic rats: alteration of guanyl nucleotide regulation.
abstract: Cardiac beta-adrenergic receptors (beta AR) were studied in rats after 4 months of diabetes induced by streptozotocin (50 mg/kg, i.v.). Saturation binding studies performed using [125I]-iodocyanopindolol (ICYP) as an antagonist ligand showed that the number and affinity of beta AR were not significantly altered. Analysis of competition curves of ICYP binding by the agonist (-)-isoproterenol showed that diabetes induces an increase in the (-)-isoproterenol IC50 and a steepening of the curve ("pseudo-Hill" coefficient not significantly different from 1) in the absence of Gpp(NH)p, while these parameters were not significantly modified in the presence of Gpp(NH)p (10(-4) M). These results indicates that beta AR were not significantly reduced in number but altered in their capacity to efficiently couple with the GTP-binding protein of adenylate cyclase (AC). These data can be correlated to the alteration of beta-adrenergic stimulation of cardiac AC previously observed after 4 months of diabetes. The characteristics of beta AR alteration at this stage of the disease are similar to those of a first step of a beta AR desensitization process due to overstimulation.
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000502:physiology*; D006165:Guanylyl Imidodiphosphate / Q000378:metabolism; D007457:Iodine Radioisotopes; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010869:Pindolol / Q000031:analogs & derivatives; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
chemical_list: D006150:Guanine Nucleotides; D007457:Iodine Radioisotopes; D011943:Receptors, Adrenergic, beta; D006165:Guanylyl Imidodiphosphate; D020120:Iodocyanopindolol; D010869:Pindolol; D007545:Isoproterenol