Stimulus-response coupling in neurohypophysial peptide target cells

1975 ◽  
Vol 55 (4) ◽  
pp. 489-536 ◽  
Author(s):  
S. Jard ◽  
J. Bockaert
Keyword(s):  
Adenylate Cyclase ◽  
Hormone Receptor ◽  
Three Dimensional ◽  
Receptor Occupancy ◽  
Enzyme Activation ◽  
Receptor Interaction ◽  
Target Cells ◽  
Mammalian Kidney ◽  
Cyclase Activation ◽  
Adenylate Cyclase Activation

Recent data on the effects of neurohypophysial peptides at the cellular level are discussed with respect to the two basic processes involved in peptide hormone action--i.e., specific recognition of the information contained in the hormonal molecule and the transformation of this information into a stimulus leading to the final biological response. Four main aspects of this general problem are considered. A. Hormone-Receptor Interaction: Recent contributions in this field concern partial analysis of the three-dimensional conformation of oxytocin and vasopressin moleculal cells of the mammalian kidney. Conformational analysis of oxytocin and vasopressin molecules leads to the conclusion that, in solution, these peptides probably have a compact and highly stabilized three-dimensional configuration. Models have been proposed that provide a valuable clue to the interpretation of structure-activity relationships among natural hormones and many structural analogues. Binding studies with tritiated oxytocin and vasopressin have permitted determination of the kinetic parameters of hormone-receptor interaction in amphibian epithelial cells and mammalian kidney. B. Stimulus Generation: The nature of the primary stimulus generated by hormone-receptor interaction is still unknown. In the epithelial target cells of the amphibian skin and bladder and of the mammalian kidney, one of the first consequences of hormone-receptor interaction is the activation of membrane-bound adenylate cyclase. Analysis of the correlations between hormonal binding and adenylate cyclase activation suggests that activation is a function of receptor occupation rather than of the number of hormonal molecules interacting with the receptor per unit of time. On medullary adenylate cyclase of pig kidney, the relation between receptor occupancy and enzyme activation was found to be complex and nonlinear. The effects of several agents (calcium, nucleotides) on receptor occupancy and adenylate cyclase activation have been described. In mammalian uterus and other smooth muscle target cells, there is no evidence for direct involvement of cyclic AMP in the contractile response to oxytocin and other neurohypophysial peptides.

Influence of pregnancy on G-protein coupling to adenylate cyclase activation in guinea-pig myometrium

1990 ◽  
Vol 127 (1) ◽  
pp. 15-21 ◽  
Author(s):  
S. J. Arkinstall ◽  
C. T. Jones
Keyword(s):  
Adenylate Cyclase ◽  
Total Activity ◽  
Enzyme Activation ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Functional Coupling ◽  
Hormonal Stimulation ◽  
Surface Receptors ◽  
Cyclase Activation ◽  
Adenylate Cyclase Activation

ABSTRACT The regulatory factors controlling uterine activity during pregnancy remain unclear in many species. Since myometrial relaxants raise intracellular cyclic AMP, modulation of signalling pathways coupling cell-surface receptors to adenylate cyclase activation could be an important site for control. To assess the functional activity of the stimulatory GTP-binding protein Gs we have measured adenylate cyclase activation by GTP, its non-hydrolysable analogue guanosine 5′-(β-γ-imido)triphosphate (Gpp(NH)p), fluoride, forskolin and manganese in a 50 000 g membrane fraction prepared from the myometrium of non-pregnant, mid-pregnant (30–32 days) and late-pregnant (62–66 days) guinea-pigs (full term 67±2 days). While forskolin- and manganese-dependent enzyme activation was unaltered by pregnancy, maximal stimulation by Gpp(NH)p and fluoride was enhanced by up to 200%. Recovery of adenylate cyclase activity in the 50 000 g fraction was essentially constant at 20–24% of the total activity throughout pregnancy, and thus cannot explain the increases observed. Since guanine nucleotides and fluoride stimulate adenylate cyclase through activating Gs, and forskolin and manganese act at the level of the catalytic unit, these data are consistent with a pregnancy-related increase in Gs functional coupling while adenylate cyclase activity is unaltered. These observations suggest a physiological regulation of myometrial Gs activity during pregnancy which could facilitate hormonal stimulation of adenylate cyclase and contribute to uterine quiescence by increasing uterine sensitivity to relaxants. Journal of Endocrinology (1990) 127, 15–21

Receptor occupancy and adenylate cyclase activation in rat liver and heart membranes by 10 glucagon analogs modified in position 2, 3, 4, 25, 27 and/or 29

1988 ◽  
Vol 21 (1-2) ◽  
pp. 117-128 ◽  
Author(s):  
Patrick Robberecht ◽  
Catherine Damien ◽  
Luis Moroder ◽  
David H. Coy ◽  
Erich Wünsch ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Rat Liver ◽  
Receptor Occupancy ◽  
Cyclase Activation ◽  
Heart Membranes ◽  
Adenylate Cyclase Activation

Mechanisms involved in alpha-adrenergic phenomena

1985 ◽  
Vol 248 (6) ◽  
pp. E633-E647 ◽  
Author(s):  
J. H. Exton
Keyword(s):  
Protein Kinase ◽  
Adenylate Cyclase ◽  
Adrenergic Receptors ◽  
Regulatory Protein ◽  
Smooth Muscles ◽  
Target Cells ◽  
Guanine Nucleotide Binding Protein ◽  
Cyclase Activation ◽  
Adenylate Cyclase Activation ◽  
Dependent Protein

Epinephrine and norepinephrine exert many important actions by interacting with alpha 1- and alpha 2-adrenergic receptors in their target cells. Activation of alpha 2-adrenergic receptors causes platelet aggregation and other inhibitory cellular responses. Some of these responses are attributable to a decrease in cAMP due to inhibition of adenylate cyclase. Activation of alpha 2-adrenergic receptors promotes their coupling to an inhibitory guanine nucleotide binding protein (Ni). This coupling promotes the binding of GTP to Ni, causing it to dissociate into subunits. This results in inhibition of the catalytic component of adenylate cyclase. Activation of alpha 1-adrenergic receptors stimulates the contraction of most smooth muscles and alters secretion and metabolism in several tissues. The primary event is a breakdown of phosphatidylinositol-4,5-bisphosphate in the plasma membrane to produce two intracellular "messengers": myo-inositol-1,4,5-trisphosphate (IP3) and 1,2-diacylglycerol (DAG). IP3 causes the release of Ca2+ from endoplasmic reticulum, producing a rapid rise in cytosolic Ca2+. Ca2+ binds to the regulatory protein calmodulin, and the resulting complex interacts with specific or multifunctional calmodulin-dependent protein kinases and other calmodulin-responsive proteins, altering their activities and thereby producing a variety of physiological responses. DAG also produces effects by activating a Ca2+-phospholipid-dependent protein kinase (protein kinase C) that phosphorylates and alters the activity of certain cellular proteins. Frequently there is synergism between the IP3 and DAG mechanisms.

REGULATION OF RECEPTOR-OPERATED Ca2− CHANNEL OPENING IN HUMAN PLATELETS

1987 ◽  
Author(s):  
Katrina J Moffat ◽  
D Euan MacIntyre
Keyword(s):  
Adenylate Cyclase ◽  
Contrast Agents ◽  
Guanylate Cyclase ◽  
Receptor Occupancy ◽  
Human Platelets ◽  
Regulatory Mechanisms ◽  
Receptor Interaction ◽  
Thrombin Receptors ◽  
Channel Opening ◽  
Camp And Cgmp

Agonist-induced elevation of the platelet intracellular free Ca2+ concentration ([Ca2−]i), as monitored using quin2, is not electrically mediated and is attenuated by removal of extracellular Ca2− and by lanthanides (e.g Gd3−).Collectively these data suggest that elevation of [Ca2−]i in platelets derives in part via influx of external Ca2−presumably through a receptor-operated Ca2− channel (ROC). Hal lam & Rink (FEBS Lett. 186: 175: 1985) showed that Mn2−also enters platelets via these ROC. To investigate the possible regulatory mechanisms that govern ROC status, we utilized quin2-labelled human platelets suspended in a Ca2+-free Hepes buffered Tyrodes solution, and monitored agonist-induced Mn2+-mediated quenching of quin2 fluorescence as an index of ROC opening.Thrombin (Th, 0.01-1 U/ml), Vasopressin (VP, 10-1000 nM) and the TxA2-mitnetic, EP171 (1-100 nM) all induced ROC opening which occurred rapidly (<30s), was maximal within 30-60s and thereafter declined. Gd3+ (≤2 mM) markedly impaired this Mn2ࢤ-mediated quenching of quin2 fluorescence induced by all 3 agonists. The adenylate cyclase stimulant PGD2 (3-3000 nM) and the guanylate cyclase stimulant sodium nitroprusside (0.01-10 μM) impaired ROC opening induced by Th (0.5 U/ml), VP (100 nM) and EP171 (25 nM) whether added to platelets ≤120sbefore or 30s after the agonists. In contrast, agents that selectively antagonize, at the receptor level, the effects of VP (e.g. d(CH2)5Tyr Me AVP, 10 ¼H) or EP171 (e.g.EP092, 250nM), or that inhibit the action of Th(e.g. Hirudin 1 U/ml)only impaired ROC opening when added to platelets simultaneously with or before the agonist.These results indicate that, although initiated by agonist-receptor interaction, maintenance of the open state of ROC in human platelets does not require continued receptor occupancy or activation by agonist. Moreover, besides acting to impair the transduction processes initiated following occupancy by agonist of platelet Vi, TP and Thrombin receptors, cAMP-and cGMP-dependent reactions also can terminate or otherwise limit opening of ROC.

scholarly journals Effects of Topical Adenosine Analogs and Forskolin on Rat Pial Arterioles in vivo

1991 ◽  
Vol 11 (1) ◽  
pp. 72-76 ◽  
Author(s):  
Setsuro Ibayashi ◽  
Al C. Ngai ◽  
Joseph R. Meno ◽  
H. Richard Winn
Keyword(s):  
Adenylate Cyclase ◽  
Adenosine Analogs ◽  
Cyclase Activation ◽  
Window Technique ◽  
Adenylate Cyclase Activation ◽  
Pial Arterioles ◽  
Adenosine Agonists ◽  
Cerebral Vasodilation

We utilized the closed window technique to study the in vivo responses of rat pial arterioles to superfused adenosine agonists. Adenosine and its analogs dilated pial arterioles and exhibited the following order of potency: 5′ N-ethylcarboxamide adenosine (NECA) > 2-chloroadenosine (2-CADO) > adenosine = R-N6-phenylisopropyladenosine ( R-PIA) = S-PIA > N6-cyclohexyladenosine (CHA). This potency profile suggests that cerebral vasodilation is mediated through the A2 receptor. Forskolin (10−9 M) potentiated the vasodilation caused by 10−6 M NECA, thus implicating adenylate cyclase activation during NECA-induced vasodilation and providing further support for involvement of the A2 receptor.

Six git genes encode a glucose-induced adenylate cyclase activation pathway in the fission yeast Schizosaccharomyces pombe

1993 ◽  
Vol 105 (4) ◽  
pp. 1095-1100 ◽  
Author(s):  
S.M. Byrne ◽  
C.S. Hoffman
Keyword(s):  
Adenylate Cyclase ◽  
Schizosaccharomyces Pombe ◽  
Glucose Repression ◽  
Signal Transduction Pathway ◽  
Activation Pathway ◽  
Cyclase Activation ◽  
Adenylate Cyclase Activation ◽  
Before And After ◽  
Dependent Protein ◽  
Camp Levels

An important eukaryotic signal transduction pathway involves the regulation of the effector enzyme adenylate cyclase, which produces the second messenger, cAMP. Previous genetic analyses demonstrated that glucose repression of transcription of the Schizosaccharomyces pombe fbp1 gene requires the function of adenylate cyclase, encoded by the git2 gene. As mutations in git2 and in six additional git genes are suppressed by exogenous cAMP, these ‘upstream’ git genes were proposed to act to produce a glucose-induced cAMP signal. We report here that assays of cAMP levels in wild-type and various mutant S. pombe cells, before and after exposure to glucose, show that this is the case. The data suggest that the cAMP signal results from the activation of adenylate cyclase. Therefore these ‘upstream’ git genes appear to encode a glucose-induced adenylate cyclase activation pathway. Assays of cAMP on a strain carrying a mutation in the git6 gene, which acts downstream of adenylate cyclase, indicate that git6 may function to feedback regulate adenylate cyclase activity. Thus git6 may encode a cAMP-dependent protein kinase.

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