Structure-binding—Activity analysis of beta-adrenergic amines—I

Bilezikian, John P.; Dornfeld, Alan M.; Gammon, Donald E.

doi:10.1016/0006-2952(78)90100-4

Cited by 49 publications

(7 citation statements)

References 24 publications

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“…ACA of cell homogenate was determined in a reaction mixture containing in final concentration: 50 μM [α‐ 32 P]‐ATP, 5 mM MgCl 2 , 30 mM KCl, 27 mM theophyline, 100 μM ATP, 0.1 mM EDTA, 0.1 mM cAMP, 5 mM creatine phosphate, 0.4 ng/ml creatine kinase, and 50 mM Tris‐HCl (pH 7.5) in a total volume of 100 μl containing tracer amounts of [ 3 H cAMP], as previously described (Bilezikian et al, 1978; Glusman et al, 1993). The reaction was started by addition of the cell homogenate (50 μg/tube) and incubated at 31°C for 20 min.…”

Section: Methodsmentioning

confidence: 99%

PTH‐dependent adenylyl cyclase activation in SaOS‐2 cells: Passage dependent effects on G protein interactions

Hong

Bodine²,

Murrills³

et al. 2002

Journal Cellular Physiology

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Parathyroid hormone (PTH) sensitive adenylyl cyclase activity (ACA) in SaOS-2 cells varies as a function of cell passage. In early passage (EP) cells (< 6), ACA in response to PTH and forskolin (FOR) was relatively low and equivalent, whereas in late passage (LP) cells (> 22), PTH exceeded FOR dependent ACA. Potential biochemical mechanisms for this passage dependent change in ACA were considered. In EP, prolonged exposure to pertussis toxin (PT) markedly enhanced ACA activity in response to PTH, Isoproterenol and Gpp(NH)p, whereas ACA in response to FOR was decreased. In contrast, the identical treatment of LP with PT diminished all ACA in response to PTH, Gpp(NH)p, and FOR. The dose dependent effects of PT on subsequent [(32)P]ADP-ribosylation of its substrates, GTPase activity, as well as FOR-dependent ACA, were equivalent in EP and LP. The relative amounts of G(alpha)i and G(alpha)s proteins, as determined both by Western blot, PT and cholera toxin (CT) dependent [(32)P]ADP-ribosylation, were quantitatively similar in EP and LP. Western blot levels of G(alpha)s and G(alpha)i proteins were not influenced by prior exposure to PT. Both PT and CT dependent [(32)P]ADP-ribosylation were dose-dependently decreased following exposure to PT. However, the PT-dependent decline in CT-dependent [(32)P]ADP-ribosylation occurred with enhanced sensitivity in LP. The protein synthesis inhibitor cycloheximide partially reversed the PT associated decrease in FOR dependent ACA in EP. In contrast, cycloheximide completely reversed the PT associated decrease in FOR and as well as PTH dependent ACA in LP. G(alpha)s activity, revealed by cyc(-) reconstitution, was not altered either by cell passage or exposure to PT. The results suggest that the coupling between the components of the complex may be pivotally important in the differential responsiveness of early and late passage SaOS-2 cells to PTH.

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Section: Methodsmentioning

confidence: 99%

PTH‐dependent adenylyl cyclase activation in SaOS‐2 cells: Passage dependent effects on G protein interactions

Hong

Bodine²,

Murrills³

et al. 2002

Journal Cellular Physiology

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“…As a general rule, isoproterenol analogs in which the meta-OH is retained and the para-OH is replaced by a "OH-simulating" group are $-adrenoreceptor antagonists or they are only very weak agonists (26,27 of an ordered water crust that interacts with adenylate cyclase to induce a specific and highly favored conformational perturba tion of this enzyme that may be involved in 3-adrenergic receptor actions (76,77,78). In fact, structure-activity relationships based on measurement of the ability of catecholamines to bind to the 3-receptor 'and activate or inhibit adenylate cyclase in mem branes of turkey erythrocytes corresponds closely with those derived using guinea pig tissue (79,80). In a search for new selective 3-adrenergic bronchodilators a series of catecholamine analogs bearing a substituted amino func tionality in the meta position was investigated (30).…”

Section: Modification Of the Catechol Systemmentioning

confidence: 59%

New Aspects of β-Adrenergic Bronchodilator Drugs

Kaiser¹

1980

ACS Symposium Series

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Although bronchoconstriction caused by contraction of bron chiolar muscles is only one of several factors involved in asthma, drugs that induce relaxation of these muscles are frequently used in therapy. Agents that cause bronchiolar muscle relaxation may act by several different modes as suggested by the biochemical mechanism of smooth muscle relaxation (1). Such agents include a group of adrenergic receptor agonists. In mild and occasional episodic asthma, bronchoconstriction and its resultant symptoms are easily reversed by administration of effective β-adrenorecep tor activators. Such agents also find some utility in alleviation of respiratory distress in emphysema and bronchitis. Some more recent aspects of such adrenergic bronchodilators, i.e., compounds that are structurally related to the natural hormones and neuro transmitters norepinephrine (1a) and epinephrine (1b), are the subject of this review.Classification of adrenergic receptors into α and β subtypes (2) is now generally accepted. On the basis of differences in response to selective agonists (3, 4, 5) and antagonists (6, 7), Lands and his associates (3, 4, 5, 8) further subdivided the β receptors into two groups, i.e., β 1 and β 2 -drenoreceptors. Acti vation of β 2 -drenoreceptors causes relaxation of smooth muscle in bronchi, uterus and vasculature, decreases tension in some skele tal muscle, and mediates glycolysis and glycogenolysis.Responses mediated by interaction with 3i~adrenoreceptors are increased force and rate of contraction of cardiac muscle, dilation of coro nary blood vessels (9, 10), relaxation of smooth muscle in the alimentary tract, and lipolysis.Epinephrine, administered either by injection or inhalation, is still employed to relieve bronchoconstriction in bronchial asthma. Isoproterenol (lc), the prototype of 3-adrenergic recep tor agonists, because of its greater potency and selectivity has largely replaced epinephrine as an inhaled bronchodilator. This synthetic analog of epinephrine also lacks selectivity.It is almost equally effective in activating both βχ and $2~a c * rener gi c receptors. Thus, it not only produces a powerful bronchodilating 0-8412-0536-l/80/47-118-251$08.25/0

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“…27, No. 8, 2016 by Bilezikian et al 19 Close inspection of the compounds listed in Figure 1, in particular compounds 6-9 demonstrated what could be considered most of the first tranche of molecules with β 1 activities, directed predominately against cardiac disease. The time lines for individual agents with "specificity" overlap however, since compounds with β 2 activities, directed against bronchial tissue, and thus often used in the treatment of asthma, were identified relatively early on with examples being compounds 10 to 13 and the levoisomer of 10, compound 17, being approved in 2000.…”

Section: β-Agonistsmentioning

confidence: 96%

“…Salmeterol (16) was the first approved agent that demonstrated that the amino group on the side chain could be radically extended and still maintain agonist activity and ring structures on both sides of the basal structure could also maintain activity as demonstrated by the very recent approval of olodaterol (18). 20 The even more complex agent batefenterol (19) only has small components of the base pharmacophore in two dimensions, where it would be very interesting to see a crystal structure of this molecule in the agonist pocket, is currently in Phase II clinical trials and also demonstrates muscarinic activity. 21 Finally in the β 2 "family", is the very interesting dihydroxy dihydroisoquinoline alkaloid, higenamine (20) isolated from the leaves of Nandina domestica, 22 which brings an interesting aspect to the relationship of the side chain amine and a hydroxyl group.…”

Section: β-Agonistsmentioning

confidence: 99%

Natural Product-Derived Drugs Based on β-Adrenergic Agents and Nucleosides

Newman¹

2016

Journal of the Brazilian Chemical Society

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This relatively short review demonstrates the very important role of the structures of the natural products adrenaline and relatives, in the design and subsequent approval of β-agonists and antagonists, and of modified nucleosides as anticancer, and in particular, antiviral agents against herpes (HSV), human immunodeficiency virus (HIV) and hepatitis C virus (HCV) that would not have been synthesized in the absence of knowledge of bioactive arabinose nucleosides.

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Structure-binding—Activity analysis of beta-adrenergic amines—I

Cited by 49 publications

References 24 publications

PTH‐dependent adenylyl cyclase activation in SaOS‐2 cells: Passage dependent effects on G protein interactions

PTH‐dependent adenylyl cyclase activation in SaOS‐2 cells: Passage dependent effects on G protein interactions

New Aspects of β-Adrenergic Bronchodilator Drugs

Natural Product-Derived Drugs Based on β-Adrenergic Agents and Nucleosides

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