Does treatment with beta‐adrenoceptor antagonists in vivo alter human adenylate cyclase responsiveness in vitro?

Michel, Miriam; Klüppel, Ma. Lúcia W.; Philipp, Thomas; Brodde, O.‐E.

doi:10.1111/j.1365-2125.1991.tb05620.x

Cited by 2 publications

(2 citation statements)

References 17 publications

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“…PRO significantly reduced the platelet content of P1,P4-Di(adenosine-51) tetraphosphate, while MET did not do so [110]. Neither treatment with or withdrawal of any of theadrenoceptor antagonists PRO, bisoprolol (BIS), ICI 118.551 and PIN altered adenylate cyclase responsiveness of blood platelets in healthy volunteers [111]. No effects on the platelet activities of NTPDase (apyrase) and 5'-nucleotidase were observed when pharmacological doses of PRO were administered to hypertensive and diabetic/hypertensive patients [112].…”

Section: Cyclic Nucleotides and Bab Drugsmentioning

confidence: 84%

“…Administration of bevantolol (BEV) after calcium ionophore A23187, stepwise and significantly declined aggregation of platelets [23]. Pretreatment with metoprolol (MET) in a dose resulting in "therapeutic" plasma levels significantly reduced platelet accumulation of radioactivity from 111 In-labelled platelets on the wall of the thoracic aorta, at intercostal artery and at coronary artery bifurcations [24].…”

Section: In Vitro Studies Bab Drugs and Platelet Aggregationmentioning

confidence: 98%

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Antiplatelet and Antileukocyte Effects of Cardiovascular,Immunomodulatory and Chemotherapeutic Drugs

Nosáľ¹

2006

CHAMC

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In vitro and ex vivo interactions of betaadrenoceptor blocking drugs, antihistamines and chloroquine with blood platelets and polymorphonuclear leukocytes resulted in different alterations of regulatory functions of these blood cells. Inhibition of platelet aggregation, arachidonate regulatory pathway, 5-hydroxytryptamine transportation, removal of platelet membrane receptors, inhibition of second messenger pathways at subcellular level and suppression of phagocytosis are indicative of nonreceptor rather than specific receptor interactions. Binding of drugs with biomembranes is reversible depending on the ionic charge of the molecule and hydrophobicity of the bilayer, partition coefficient, pH and pKa of the amphiphilic molecules and other physico-chemical properties of amphiphilic drugs. Alterations in the drug molecule structure alters the drug-phospholipid binding profile. Any change in the metabolism of membrane phospholipids directly or indirectly influences one or more of the important components of the phospholipid-signalling pathway. In addition to changes in phospholipase A, C and D activities, protein kinase C, calmodulin-phosphodiesterase, Ca2+,Mg2+-ATPase, Na+,K+-ATPase and other messengers were found to be changed in cells and tissue after cationic amphiphilic drug (CAD) administration. Although not much has been understood of the mechanism by which some CAD affect immune functions, there are good reasons to suggest that these effects might occur. CADs share sufficient similarities in their structure even though they come from diverse pharmacological classes. CADs affect ion transport, immune functions, tumour growth, serotonin metabolism and several other functions in the body. Extensive therapeutic use and associated side effects have generated a great deal of interest in understanding the nonreceptor interactions with CADs.

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Section: Cyclic Nucleotides and Bab Drugsmentioning

confidence: 84%

Section: In Vitro Studies Bab Drugs and Platelet Aggregationmentioning

confidence: 98%

Antiplatelet and Antileukocyte Effects of Cardiovascular,Immunomodulatory and Chemotherapeutic Drugs

Nosáľ¹

2006

CHAMC

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Actions of Lithium on the Cyclic AMP Signalling System in Various Regions of the Brain ‐ Possible Relations to its Psychotropic Actions ‐: A Study on the Adenylate Cyclase in Rat Cerebral Cortex, Corpus Striatum and Hippocampus

Mørk

1993

Pharmacology & Toxicology

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It has been estimated that in most industrialized countries 1 person out of every 1000 in the population is undergoing lithium treatment to stabilize their episodic mood disturbances due to manic-depressive illness. Lithium may stabilize mood swings by altering the action of certain neurotransmitters at the synaptic level in the brain. Recent research suggests that lithium alters neurotransmission by affecting neurotransmitter-coupled second messenger systems. A major second messenger system is the adenylate cyclase, which generates intracellular cAMP from ATP. The adenylate cyclases (type I-IV) are regulated by stimulatory and inhibitory receptors, which either stimulate or inhibit the adenylate cyclase activity. The stimulatory and inhibitory neurotransmitter-receptor signals are transferred to the catalytic unit of the adenylate cyclase by Gs and Gi, respectively. The activated receptor induces GTP stimulation of the heterotrimeric G protein, leading to a dissociation of the protein into the active alpha*GTP and the beta gamma complex. The former stimulates the catalytic unit of adenylate cyclase. The stimulation is terminated by a GTPase located on the alpha subunit that converts GTP to inactive GDP. At present, G proteins are known to play a central role in coupling receptors to effector proteins. In addition to extracellular regulation due to neurotransmitters, some adenylate cyclases (type I, III) are regulated by CaM as a consequence of enhanced intracellular concentrations of free Ca2+. The Ca(2+)-dependent stimulation of adenylate cyclase by CaM is assumed to occur by a direct effect on the catalytic unit. The catalytic units sensitive to Ca(2+)-CaM are also subjected to regulation by stimulatory and inhibitory neurotransmitter stimuli. Magnesium is essential for adenylate cyclase activity, since MgATP2- is the enzyme substrate. Furthermore, one Mg2+ site located on the G protein regulates both the receptor agonist affinity and the dissociation of the G protein during the activation cycle. A second Mg2+ site on the catalytic unit is responsible for Mg2+ regulation of the catalytic activity. The present work aimed at investigating the mechanisms by which lithium in vitro and after chronic treatment (ex vivo) affects adenylate cyclase activities in various regions of the rat brain. Lithium in vitro and ex vivo inhibited the selective stimulation of adenylate cyclase by Ca(2+)-CaM in the cerebral cortex. Furthermore, lithium in vitro interacted directly with the catalytic unit of adenylate cyclase.(ABSTRACT TRUNCATED AT 400 WORDS)

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Does treatment with beta‐adrenoceptor antagonists in vivo alter human adenylate cyclase responsiveness in vitro?

Cited by 2 publications

References 17 publications

Antiplatelet and Antileukocyte Effects of Cardiovascular,Immunomodulatory and Chemotherapeutic Drugs

Antiplatelet and Antileukocyte Effects of Cardiovascular,Immunomodulatory and Chemotherapeutic Drugs

Actions of Lithium on the Cyclic AMP Signalling System in Various Regions of the Brain ‐ Possible Relations to its Psychotropic Actions ‐: A Study on the Adenylate Cyclase in Rat Cerebral Cortex, Corpus Striatum and Hippocampus

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