Adenosine antagonists

Williams, Michael

doi:10.1002/med.2610090205

Cited by 42 publications

(16 citation statements)

References 118 publications

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“…The potency order of adenosine analogues in hyperpolarizing the SCG and inhibiting the depolarization caused by muscarine was characteristic of that generally observed for Al-adenosine receptor agonists and differed markedly from the order characteristic of A2-adenosine receptor agonists as outlined in the Introduction and as described and reviewed by Williams (1989). Both the absolute potency and relative order of potency of adenosine analogues in hyperpolarizing ganglia are similar to values reported for tissues containing Al-adenosine receptors (Daly, 1982).…”

Section: Discussionsupporting

confidence: 57%

“…More recently the relative affinity of N6-substituted adenosine analogues in binding studies has been examined by Daly et al (1986) and Ukena et al (1987) and it was proposed that the adenosine receptor analogues 5'-N-ethylcarboxamidoadenosine (NECA), N6-cyclohexyladenosine (CHA), N6-cyclopentyladenosine (CPA), R( + )and S(-)-N6-phenyl-isopropyladenosine (R-PIA and S-PIA), 2-chloroadenosine (2CA) and 2-phenylaminoadenosine (PAA) would be useful in functional studies for defining receptor subtypes. In both functional studies and binding studies a potency order of adenosine analogues for A,-adenosine receptors was CPA > R-PIA > 2CA > NECA > S-PIA > PAA and for A2adenosine receptors was NECA > 2CA > PAA = R-PIA > CPA > S-PIA (Williams, 1989).…”

Section: Introductionmentioning

confidence: 93%

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Characterization of the adenosine receptors of the rat superior cervical ganglion

Connolly

Stone

Brown

1993

British J Pharmacology

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1 Adenosine analogues caused hyperpolarization and inhibition of the depolarizing response to muscarine of the rat isolated superior cervical ganglion (SCG) measured by a 'grease gap' recording technique. The receptors mediating these responses have been characterized by use of a range of selective adenosine analogues and adenosine receptor antagonists. 2 In decreasing order of potency N6-cyclopentyladenosine (CPA), 2-chloroadenosine (2CA), adenosine, 2-phenylaminoadenosine (PAA), caused concentration-dependent hyperpolarizations whilst N6-(9-fluorenylmethyl)adenosine (PD 117,413) was inactive at up to 100 1M.3 The order of potency of adenosine analogues in depressing depolarization caused by a submaximal concentration of muscarine (100 nM) was: CPA> R-PIA = 2CA> NECA> S-PIA> BZA > adenosine> PAA, where R-and S-PIA = R(-)-and S(+)-N6-(2-phenylisopropyl)adenosine, NECA = 5'Nethylcarboxamidoadenosine and BZA = N6-benzyladenosine. PD 117,413 was inactive at concentrations up to 100 JIM. The maximum inhibitions of the muscarine-induced depolarization by CPA, 2CA, NECA and BZA were similar. R-PIA, S-PIA and PAA produced similar maximal inhibitions which were significantly smaller than those produced by CPA. 4 Hyperpolarizations caused by adenosine were antagonized by the P1-purinoceptor selective antagonist 1,3-dimethyl-8-phenylxanthine (8PT) and by the selective Al-adenosine receptor antagonist, 1,3-dipropyl-8-(4-((2aminoethyl)amino)carbonylmethyloxyphenyl)xanthine (XAC). Hyperpolarizations caused by CPA, adenosine and PAA were antagonized by the Al-selective antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) but not by the A2-selective antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX). 5 Inhibition of the muscarinic-induced depolarization by CPA was antagonized by 8PT and DPCPX but not by DMPX.6 It is concluded that the neurones of the rat SCG possess PI-purinoceptors of the Al-adenosine receptor subtype which mediate hyperpolarization and inhibition of depolarization caused by muscarine.

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Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 93%

Characterization of the adenosine receptors of the rat superior cervical ganglion

Connolly

Stone

Brown

1993

British J Pharmacology

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“…Also, the nonselective adenosine receptor antagonist, 8-SPT (which does not cross the blood-brain barrier; Evonuik et al, 1986) was ineffective in attenuating hypotensive responses to adenosine analogues in these experiments. 8-SPT has a far lower potency than 8-PT at adenosine Al receptors (Williams, 1989), and hence a comparison of potencies must take this into account. However, since 8-SPT was ineffective in these experiments and the doses of agonists used were insufficient to produce peripheral responses of this magnitude, it is unlikely that the effects of the adenosine agonists are occurring peripherally.…”

Section: Discussionmentioning

confidence: 99%

Functional characterization of adenosine receptors in the nucleus tractus solitarius mediating hypotensive responses in the rat

White

Rose’Meyer

Hope

1996

British J Pharmacology

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1The aim of this study was to characterize adenosine receptors located in the nucleus tractus solitarius (NTS) that mediate decreases in blood pressure in the anaesthetized rat. To determine the adenosine receptor subtype involved, a range of selective agonists and antagonists were studied and their relative potencies evaluated. 2 The rank order of agonist potency in inducing decreases in diastolic blood pressure was N6-3 The hypotensive action of CPA following microinjection into the NTS was antagonized by i.v. infusions (50 Mug kg-' min-') of adenosine receptor antagonists, 8-cyclopentyl-1,3 dipropylxanthine (DPCPX), 8-phenyltheophylline (8-PT), 8-(p-sulphophenyl)theophylline (8-SPT), and 1,3-dipropyl-8-N-(2-(diethylamino)ethyl)-N methyl-4-(2,3,6,7-tetrahydro-2,6-dioxo) benzenesulphonamidexanthine (PD 115199). The antagonist potency order was DPCPX>PD115199 >8-PT. Intravenous infusion of 8-SPT had no effect on blood pressure responses to microinjection of CPA into the NTS.4 The results suggest that adenosine Al receptors in the NTS mediate hypotensive responses in the anaesthetized rat preparation.

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“…In organs or cell preparations, the R-PIA dose-response curve depicting cAMP production may be biphasic, characterized by inhibition of adenylate cyclase activity in the nanomolar range and by stimulation of CAMP production at micromolar concentrations. Compared with R-PIA, NECA is a more potent activator of the A2-site which stimulates adenylate cyclase and does not show inhibitory activity on this enzyme (Londos et al, 1980;Williams, 1989).…”

Section: Discussionmentioning

confidence: 99%

Adenosine receptors, cyclic AMP accumulation, and DNA‐synthesis in aortic smooth muscle cell cultures of adult and neonatal rats

Querol‐Ferrer¹,

Hultgårdh‐Nilsson

Ringertz

et al. 1992

Journal Cellular Physiology

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The effects of two adenosine analogs on cyclic AMP (cAMP) accumulation and DNA synthesis were studied in cultured smooth muscle cells (SMCs) isolated from adult and neonatal rat arteries. N-ethylcarboxamido adenosine (NECA) dose-dependently increased intracellular cAMP levels and appeared to be more potent in adult than in neonatal SMCs. R-phenylisopropyl adenosine (R-PIA), in nanomolar concentrations, counteracted the increase in cAMP evoked by 10 microM forskolin in adult but not in neonatal SMCs, indicating that the enhanced "A2" response seen in adult SMCs was not due to a lack of "A1" receptors in these cultures. Binding experiments performed using the adenosine antagonist XAC did not reveal any differences in the number or affinity of the adenosine receptors between neonatal and adult SMCs. This indicates effects presumably on the G-protein level. A high capacity to spontaneously synthesize DNA and a weak response to platelet-derived growth factor (PDGF) were seen in the neonatal SMCs. Furthermore, NECA had no effect on PDGF-induced DNA synthesis in these cells. In contrast, adult SMCs presented a low rate of spontaneous DNA synthesis and a marked proliferative response to PDGF, which was inhibited by NECA. This inhibition paralleled the increase in cAMP elicited by NECA. Our findings suggest that neonatal and adult SMCs differ both in their response to growth factors and growth inhibitors.

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Adenosine antagonists

Cited by 42 publications

References 118 publications

Characterization of the adenosine receptors of the rat superior cervical ganglion

Characterization of the adenosine receptors of the rat superior cervical ganglion

Functional characterization of adenosine receptors in the nucleus tractus solitarius mediating hypotensive responses in the rat

Adenosine receptors, cyclic AMP accumulation, and DNA‐synthesis in aortic smooth muscle cell cultures of adult and neonatal rats

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