Comparison of the potency of 8−phenyltheophylline as an antagonist at A1 and A2 adenosine receptors in atria and aorta from the guinea-pig

Collis, Michael G.; Palmer, Donald B.; Saville, Valerie L.

doi:10.1111/j.2042-7158.1985.tb05063.x

Cited by 32 publications

(28 citation statements)

References 10 publications

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“…This dual action could potentially result in a disinhibition of the effects of endogenous adenosine and the erroneous conclusion that adenosine is not involved in a response. 8-Phenyltheophylline (adenosine receptor PA2 of 6-4; Collis, Palmer & Saville, 1985) lacks any action of phosphodiesterase activity (Smellie, Davis, Daly & Wells, 1979). We have previously also shown that the present infusion rate 8-phenyltheophylline used is sufficient to produce an approximate 100-fold rightward shift in the vasodilator dose-response curve to adenosine (Collis & Nowell, 1986).…”

Section: Discussionmentioning

confidence: 82%

The role of adenosine in exercise hyperaemia of the gracilis muscle in anaesthetized cats.

Poucher¹,

Nowell²,

Collis³

1990

The Journal of Physiology

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SUMMARY1. A number of metabolites have been proposed to control the vascular tone of skeletal muscle during exercise. The present study was designed to investigate the role of adenosine in this response by determining the effect of the adenosine receptor antagonist 8-phenyltheophylline.2. The gracilis muscle of anaesthetized cats was exposed and made to contract by stimulating the obturator nerve (at 1 Hz, 5 V, 041 ms) for 20 min. Gracilis muscle blood flow and tension were measured during exercise and for 20 min following exercise. Initially this was performed in each animal during the infusion of a vehicle solution (50% polyethylene glycol 400, 50% 0'1 M-NaOH, 01 ml min' i.v.). Exercise was then repeated during infusion of either further vehicle (group I), 8-phenyltheophylline (group II) or 3-propylxanthine (group III), both at 2-7 x 107 mol min' kg-.3. In group 1 (n = 4) gracilis muscle blood flow during the first exercise period increased by 47-5 + 11-3 ml min-' (110 g)-' and gracilis muscle tension by 8-6 + 1X3 kg (100 g muscle mass)-1 at 20 min of exercise. These responses were not significantly different when repeated. 4. In group II (n = 5), blood flow increased by 46-9 + 9.9 ml min' (100 g)-1 and tension by 6-5 + 0-7 kg (100 g muscle mass)-1 during vehicle infusion. Infusion of 8-phenyltheophylline at a rate which abolished the vasodilatation response to 2-chloroadenosine, significantly reduced the muscle blood flow increase to 19-8 + 2-7 ml min' (100 g muscle mass)-1 (P < 0-05) but the tension response was unaffected (increased by 7-0+0-8 kg (100 g muscle mass)-'). 8-Phenyltheophylline did not affect gracilis muscle blood flow or tension at rest.5. Administration of 3-propylxanthine, which did not modify the vasodilatation response to 2-chloroadenosine, failed to alter the vascular responses to muscle contraction.6. These results suggest that activation of adenosine receptors can contribute to up to 40 % of the vasodilatation observed during isometric twitch contraction of the gracilis muscle of cats.

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Section: Discussionmentioning

confidence: 82%

The role of adenosine in exercise hyperaemia of the gracilis muscle in anaesthetized cats.

Poucher¹,

Nowell²,

Collis³

1990

The Journal of Physiology

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“…The interaction of PACPX with the non-selective adenosine receptor antagonist 8-phenyltheophylline (8-PT; Collis et al, 1985) was determined to ascertain whether the two xanthines acted at a common site. A control concentration-response curve was generated to 2-chloroadenosine and was repeated after exposure for 1 h to either PACPX (1OgIM) or 8-PT (1OI1M).…”

Section: Resultsmentioning

confidence: 99%

Apparent affinity of some 8‐phenyl‐substituted xanthines at adenosine receptors in guinea‐pig aorta and atria

Collis¹,

Jacobson²,

Tomkins³

1987

British J Pharmacology

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Some 8‐phenyl‐substituted, 1,3 dipropyl xanthines have previously been demonstrated to have a 20–400 fold greater affinity for A1 binding sites in rat CNS membranes than for A2 adenosine receptors in intact CNS cells from guinea‐pigs. In the present study these compounds (1,3, dipropyl‐8‐phenylxanthine: DPPX; 1,3 dipropyl‐8‐(2 amino‐4‐chlorophenyl) xanthine: PACPX; 8‐(4‐(2‐aminoethyl)amino) carbonyl methyl oxyphenyl)‐1,3‐dipropylxanthine: XAC; and d‐Lys‐XAC) together with two that have not been reported to exhibit A1‐receptor selectivity (8‐(p‐sulphophenyl)theophylline: 8‐PST; 8‐(4‐carboxy methyl oxyphenyl)‐1,3‐dipropylxanthine: XCC) have been evaluated as antagonists of the effects of 2‐chloroadenosine in two isolated cardiovascular tissues. The isolated tissues used were guinea‐pig atria (bradycardic response) and aorta (relaxation), which are thought to possess A1 and A2 adenosine receptors, respectively. All the xanthines antagonized responses evoked by 2‐chloroadenosine in both tissues but did not affect responses evoked by acetylcholine (atria) or sodium nitrite (aorta). The xanthines, 8‐PST, XAC, d‐Lys XAC, XCC and DPPX appeared to be competitive antagonists of the effects of 2‐chloroadenosine, as Schild plot slopes did not differ significantly from unity. The 1,3‐dipropyl substituted compounds had pA2 values from 6.5 to 7.4 and were more potent than the 1,3 dimethyl substituted 8‐PST (pA2 4.9 to 5). For individual xanthines, there was no difference between pA2 values obtained in the atria and in the aorta. Responses evoked by 2‐chloroadenosine in atria and aorta were antagonized to a similar degree by PACPX (1 μm). The agonist dose‐ratio evoked by 10 μm PACPX was no greater than that evoked by 1 μm of the xanthine in both tissues. This was probably a consequence of the limited aqueous solubility of PACPX. These results fail to demonstrate A1 receptor selectivity for DPPX, XAC, d‐Lys XAC or PACPX in tissues from the guinea‐pig. The A1 selectivity previously found for these compounds may therefore be due to their high affinity for binding sites in rat CNS cell membranes.

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“…Treatment with the non-selective adenosine receptor antagonist, 8-PT (Collis et al, 1985) yielded interesting results in RCMM. 8-PT produced concentration-dependent rightward shifts of the NECA curves with CR values consistent with adenosine-receptor antagonism (i.e.…”

Section: Discussionmentioning

confidence: 99%

“…8-PT produced concentration-dependent rightward shifts of the NECA curves with CR values consistent with adenosine-receptor antagonism (i.e. pKB 6.4-6.6, Collis et al, 1985 which 8-PT enhanced the contraction to NECA in RCMM remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the adenosine receptor mediating contraction in rat colonic muscularis mucosae

Reeves¹,

Coates²,

Jarvis³

et al. 1993

British J Pharmacology

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1 The objective of this study was to characterize the adenosine receptor mediating contraction in rat isolated colonic muscularis mucosae (RCMM). 2 Sequential additions of the adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA; 0.01 -10 gM) elicited reproducible, concentration-related contractions in RCMM. The effects of NECA were mimicked by the adenosine Al receptor-selective agonists cyclopentyladenosine (CPA), Rphenylisopropyladenosine (R-PIA) and N-[1S, trans)2-hydroxycyclopentyl] adenosine (GR79236) and by S-PIA (the stereoisomer of R-PIA). The adenosine A2 agonists N-[(2-methylphenyl)methyl] adenosine (metrifudil) and 2-[p-(2-carboxyethyl)phenethylamine]-5'-N-ethylcarboxamidoadenosine (CGS21680) also produced contractions in RCMM but were 54 and 165 times less potent respectively than NECA. The rank order of agonist potency for contraction of RCMM was CPA > GR79236 = R-PIA ) NECA> >S-PIA = metrifudil > CGS21680, which is identical to that reported for the inhibition of spontaneous rate in rat isolated right atria and inhibition of lipolysis in rat isolated adipocytes by these same agonists. 3 R-PIA, S-PIA and metrifudil behaved as partial agonists in RCMM. 5 The contractile responses to NECA in RCMM were not affected by atropine (1 JiM), tetrodotoxin (0.3 JAM) or the P2 antagonist, suramin (100IM). 6 The present study confirms that contractions to adenosine agonists in the RCMM are mediated via adenosine Al receptors.

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Comparison of the potency of 8−phenyltheophylline as an antagonist at A1 and A2 adenosine receptors in atria and aorta from the guinea-pig

Cited by 32 publications

References 10 publications

The role of adenosine in exercise hyperaemia of the gracilis muscle in anaesthetized cats.

The role of adenosine in exercise hyperaemia of the gracilis muscle in anaesthetized cats.

Apparent affinity of some 8‐phenyl‐substituted xanthines at adenosine receptors in guinea‐pig aorta and atria

Characterization of the adenosine receptor mediating contraction in rat colonic muscularis mucosae

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