guanylyl-imidodiphosphate and Hypoxia

Glutamate significantly increased levels of spontaneous chemiluminescence (CL) in rat hippocampal slices incubated under hypoxic conditions. Although it has been previously shown that guanine nucleotides (GN) displace glutamate from several of its receptors, in our study only GMP, as well as the glutamate antagonist MK-801, was able to reverse the increase in CL provoked by glutamate. On the other hand, not only GTP or Gpp(NH)p failed to reverse the action of glutamate, but they increased CL production like glutamate. This effect of GTP/Gpp(NH)p was also reversed by GMP. We concluded that, under neurotoxic conditions, GMP acted as an antagonist and GTP or Gpp(NH)p acted as agonists of glutamate. These results reinforced the evidence of the existence of extracellular site(s) for GN and indicated a possible role for GN in excitotoxicity.

Topics: Animals; Cyclic AMP; Dizocilpine Maleate; Female; Glutamic Acid; Guanine Nucleotides; Guanosine Triphosphate; Guanylyl Imidodiphosphate; Hippocampus; Hypoxia; In Vitro Techniques; Luminescent Measurements; Rats; Rats, Wistar

Chronic hypoxia induces a hyperadrenergic state which down-regulates beta-adrenergic receptors (beta-AR) in the heart. We visualized lung beta-AR binding sites after adaptation to chronic hypoxia by autoradiography of whole lung sections labeled with 50 pM 125I-labeled pindolol. A low concentration of agonist (32 nM isoproterenol) selectively masked beta-ARs with high affinity for agonists. Total specific beta-AR binding increased twofold with hypoxia. In both the control and hypoxic lung sections, 60-70% of the beta-ARs were in a high-affinity state, which could be reversed by guanine nucleotide. Autoradiography revealed a high density of high- and low-affinity beta-AR sites in lung parenchyma, predominantly involving alveolar walls, but also the walls of airways and blood vessels. The distribution of high- and low-affinity beta-AR within the lung was qualitatively identical. Hypoxia increased beta-AR binding without affecting its distribution. The majority of the additional beta-ARs induced during adaptation to chronic hypoxia are in the high-affinity state, and are thus of probable functional significance.

Topics: Animals; Autoradiography; Chronic Disease; Guanylyl Imidodiphosphate; Hypoxia; Isoproterenol; Lung; Male; Pindolol; Rats; Rats, Wistar; Receptors, Adrenergic, beta; Reference Values; Sodium; Up-Regulation