Biomaterial Database

Guanyl nucleotide potentiation of parathyroid hormone-stimulated adenylate cyclase in chicken renal plasma membranes: a receptor-independent effect. 1981

R A Nissenson, and K O Nyiredy, and C D Arnaud

We investigated the interaction of guanyl nucleotides with the parathyroid hormone (PTH) receptor-adenylate cyclase system in chicken renal plasma membranes. Micromolar concentrations of guanosine triphosphate and its hydrolysis-resistant analog 5'-guanylimidodiphosphate [Gpp(NH)p] increased both basal and PTH-stimulated adenylate cyclase activity. The enzyme activation produced by the amino-terminal 1--34 peptide of bovine PTH [bPTH-(1--34)] was potentiated by both guanyl nucleotides, although quantitatively greater effects were seen with Gpp(NH)p. The apparent activation constant for bPTH-(1--34) stimulation of adenylate cyclase, 16 nM, was reduced to 3.7 nM in the presence of 1.0 microM Gpp(NH)p. The interaction of guanyl nucleotides with the PTH receptor was evaluated by measurement of specific 125I-labeled bPTH-(1--34) binding to chicken renal plasma membranes in the presence and absence of Gpp(NH)p. There was no effect of the guanyl nucleotide on the rate of binding or dissociation of 125I-labeled bPTH-(1--34) from its renal receptor. Scatchard analysis of steady state PTH binding revealed that 1.0 microM Gpp(NH)p had minimal effect on either the affinity of PTH receptors (Kd increased from 25 nM to 30 nM) or their number (total number of binding sites increased from 8.6 to 9.4 pmol/mg protein). Separate experiments demonstrated a concentration-dependent effect on Gpp(NH)p to decrease the apparent activation constant for bPTH-(1--34) stimulation of adenylate cyclase, with no detectable guanyl nucleotide effect on the affinity of PTH receptors. The results suggest that guanyl nucleotides may enhance the coupling of occupied PTH receptors to adenylate cyclase independent of direct nucleotide effects on renal PTH receptors.

UI	MeSH Term	Description	Entries
D007668	Kidney	Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.	Kidneys
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D010281	Parathyroid Hormone	A polypeptide hormone (84 amino acid residues) secreted by the PARATHYROID GLANDS which performs the essential role of maintaining intracellular CALCIUM levels in the body. Parathyroid hormone increases intracellular calcium by promoting the release of CALCIUM from BONE, increases the intestinal absorption of calcium, increases the renal tubular reabsorption of calcium, and increases the renal excretion of phosphates.	Natpara,PTH (1-84),PTH(1-34),Parathormone,Parathyrin,Parathyroid Hormone (1-34),Parathyroid Hormone (1-84),Parathyroid Hormone Peptide (1-34),Hormone, Parathyroid
D011956	Receptors, Cell Surface	Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.	Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D002462	Cell Membrane	The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.	Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D002645	Chickens	Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA.	Gallus gallus,Gallus domesticus,Gallus gallus domesticus,Chicken
D006160	Guanosine Triphosphate	Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety.	GTP,Triphosphate, Guanosine
D006165	Guanylyl Imidodiphosphate	A non-hydrolyzable analog of GTP, in which the oxygen atom bridging the beta to the gamma phosphate is replaced by a nitrogen atom. It binds tightly to G-protein in the presence of Mg2+. The nucleotide is a potent stimulator of ADENYLYL CYCLASES.	GMP-PNP,GMP-P(NH)P,Gpp(NH)p,Guanosine 5'-(Beta,Gamma-Imido)Triphosphate,Guanyl-5'-Imidodiphosphate,P(NH)PPG,Guanyl 5' Imidodiphosphate,Imidodiphosphate, Guanylyl
D000262	Adenylyl Cyclases	Enzymes of the lyase class that catalyze the formation of CYCLIC AMP and pyrophosphate from ATP.	Adenyl Cyclase,Adenylate Cyclase,3',5'-cyclic AMP Synthetase,Adenylyl Cyclase,3',5' cyclic AMP Synthetase,AMP Synthetase, 3',5'-cyclic,Cyclase, Adenyl,Cyclase, Adenylate,Cyclase, Adenylyl,Cyclases, Adenylyl,Synthetase, 3',5'-cyclic AMP
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia