Effect of adenosine and its analogues on calcium influx in coronary artery

Ramagopal, Mudumbi V.; Mustafa, S. Jamal

doi:10.1152/ajpheart.1988.255.6.h1492

Cited by 13 publications

(12 citation statements)

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“…On the other hand, both dila zep and lidoflazine produced much less re laxing effect on the PGF2a-induced contrac tions compared with K+-induced contrac tions (tables I, II). This is further supported by the fact that we have recently shown that the influx of calcium induced by receptor activation was more sensitive to the inhibi tion by adenosine and its analogs than the calcium influx induced by membrane depo larization in coronary smooth muscle [22], The findings that the relaxation produced by dilazep, lidofiazine and diltiazem of K+ (50 mmol/l)-depolarized cerebral artery con tracted by 2.5 mmol/1 CaCl2 was unaffected by adenosine deaminase (data not shown), and that the relaxing effects of dilazep, lido fiazine and diltiazem in renal artery con tracted by PGF2a were also not affected by adenosine deaminase, suggest that the relax ations induced by these drugs were indepen dent of endogenous adenosine.…”

Section: Discussionmentioning

confidence: 71%

Relaxing Effects of Dilazep and Lidoflazine in Dog Cerebral and Renal Arteries Independent of Adenosine

Mustafa¹,

Nakagawa²

1988

Pharmacology

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The adenosine potentiating drugs dilazep and lidoflazine were studied for their relaxing ability in isolated dog cerebral and renal arteries contracted under conditions which induce the opening of potential-dependent calcium channels (using K⁺ at 30, 50 and 100 mmol/l) and under conditions which induce the opening of receptor-operated calcium channels (prostaglandin F2_α, PGF2_α; 5-hydroxytryptamine, 5-HT) and compared with those of adenosine and a standard calcium entry blocker, diltiazem. Dilazep, lidoflazine and diltiazem exerted concentration-dependent relaxation in cerebral and renal artery ring strips contracted with 30, 50 and 100 mmol/l K⁺. However, dilazep was slightly more potent at 100 mmol/l K⁺. In contrast, whereas the high concentration of adenosine (1 × 10^–5–3.7 × 10^–4 mol/l) relaxes these arteries only at 30 mmol/l K⁺, it produced a more pronounced concentration-dependent relaxation when PGF2_α or 5-HT was used as a contracting agent. The order of relaxing responses of both cerebral and renal arterial ring strips contracted by PGF201 were: diltiazem > adenosine > lidoflazine > dilazep. On the other hand, the relaxing responses on cerebral and renal arteries contracted with 5-HT were: diltiazem > lidoflazine > adenosine > dilazep and diltiazem > adenosine > lidoflazine > dilazep, respectively. Adenosine deaminase reversed the relaxation produced by adenosine, but was unable to reverse the relaxing responses to diltiazem, lidoflazine and dilazep. These findings suggest that dilazep and lidoflazine have a direct relaxing effect independent of adenosine in cerebral and renal artery ring strips possibly through their calcium entry blocking activity. The data suggest that adenosine is more effective on the receptor-operated contractions, whereas dilazep and lidoflazine are more effective on the potential-dependent contractions.

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Section: Discussionmentioning

confidence: 71%

Relaxing Effects of Dilazep and Lidoflazine in Dog Cerebral and Renal Arteries Independent of Adenosine

Mustafa¹,

Nakagawa²

1988

Pharmacology

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“…Previous studies have shown that NECA has little effect on contractions dependent upon calcium in¯ux through voltageoperated calcium channels, for example by increasing K (Young & Merrill 1983;Urquhart & Broadley 1991). Furthermore, K -induced in¯ux of 45 Ca 2 in bovine coronary artery rings (Ramagopal & Mustafa 1988) and rabbit aorta (Zawadzki & Weiss 1990) was relatively resistant to inhibition by adenosine and NECA. NECA seems, therefore, to inhibit phenylephrine-induced contractions by preventing in¯ux of extracellular Ca 2 through the so-called receptor-operated calcium channels.…”

Section: Effects Of Neca On Contractions Dependent Upon Extracellularmentioning

confidence: 91%

“…In the current study, extracellular A 2B -adenosine receptor stimulation of the guinea-pig aorta was studied by use of both adenosine and 5 H -(N-ethylcarboxamido)adenosine (NECA), which is not a substrate for the purine transport system (Collis & Brown 1983) and does not, therefore, exert an intracellular action. Stimulation of A 2 -adenosine receptors is thought to evoke vasorelaxation by reducing the amount of calcium available for contraction (Young & Merrill 1983;Ramagopal & Mustafa 1988;Zawadzki & Weiss 1990), possibly by inhibition of membrane receptor-operated calcium channels (Collis & Brown 1983;Ramagopal & Mustafa 1988;Urquhart & Broadley 1991), resulting in reduced entry of extracellular calcium ions. Previous studies have shown that adenosine inhibits both intra-and extracellular Ca 2 mobilization in the relaxation of coronary arteries precontracted with PGF 2a , acetylcholine or noradrenaline (Ramagopal et al 1989;Ramagopal & Mustafa 1990).…”

mentioning

confidence: 99%

Differences between the Vasorelaxant Activity of Adenosine-receptor Agonists on Guinea-pig Isolated Aorta Precontracted with Noradrenaline or Phenylephrine

Ford

Maddock

Buckingham³

et al. 1999

Journal of Pharmacy and Pharmacology

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The relaxant effect of adenosine and 5'-(N-ethylcarboxamido)adenosine (NECA) against alpha-adrenoceptor-mediated contractile tone in guinea-pig isolated aortic rings has been examined to determine if this A2B-receptor-mediated relaxation was dependent upon the contracting agent, and whether the contractions were dependent upon intracellular or extracellular calcium. Relaxation responses were consistently greater for aortic rings pre-contracted with phenylephrine (3x10(-6) M) than for rings pre-contracted with noradrenaline (3x10(-6) M). Maximum inhibition by NECA was significantly greater for phenylephrine-contracted aortae than for noradrenaline-contracted (81.9+/-2.8% compared with 25.0+/-1.5%). These differences persisted in the presence of beta- and alpha2-adrenoceptor blockade and could not, therefore, be attributed to stimulation of these receptors by noradrenaline. The ratio of the contractions obtained before and in the presence of adenosine or NECA was compared with the control ratio obtained before and after vehicle. Experiments were performed both in the presence of normal calcium levels and under calcium-free conditions. In normal-calcium medium, NECA inhibited phenylephrine-induced contractions (test ratio, 76.7+/-3.9%; control ratio, 133.1+/-9.8%) to a greater extent than noradrenaline-induced contractions (108.4+/-4.1 and 123.4+/-4.9%); adenosine similarly inhibited phenylephrine-induced contractions more than those induced by noradrenaline. Under calcium-free conditions, adenosine (36.7+/-11.9 and 110.7+/-26.6%) and NECA (55.2+/-9.1 and 87.1+/-14.9%) were only effective against phenylephrine-induced contractions. This suggests that activation of the A2B-receptor by these agonists inhibited intracellular mobilization of calcium for phenylephrine-induced contractions only. The effects on extracellular calcium influx were examined for phenylephrine- and noradrenaline-induced contractions in normal-calcium medium but in the presence of ryanodine to prevent intracellular calcium mobilization. NECA inhibited phenylephrine-induced contractions (77.3+/-12.4 and 111.4+/-9.3%), presumably by interfering with influx of calcium through receptor-operated calcium channels. In contrast, NECA failed to reduce noradrenaline-induced contractions (121.5+/-10.7 and 122.4+/-11.6%), suggesting that the effect on noradrenaline is predominantly via interaction with intracellular calcium. Adenosine was consistently a more effective relaxant than NECA, possibly because of an additional intracellular component of the response. We conclude that adenosine receptor agonists inhibit phenylephrine-induced contractions of guinea-pig aorta more selectively than noradrenaline-induced contractions. A2B-receptor stimulation might reveal a fundamental difference between the modes of contraction elicited by these two alpha-adrenoceptor agonists.

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“…Endothelium-derived NO thus partly mediates the vasodilator effects of adenosine. Adenosine has also been shown to result in stimulation of K +ATP channels, leading to hyperpolarization of smooth muscle [12] and to decrease the entry of calcium into vascular smooth muscle leading to vasodilation [13].…”

Section: Introductionmentioning

confidence: 99%

Improved Oxygenation following Adenosine Infusion in Persistent Pulmonary Hypertension of the Newborn

et al. 1998

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Six consecutive cases of persistent pulmonary hypertension of the newborn (PPHN) were treated with adenosine following failure of conventional therapy, excluding inhaled nitric oxide. A rise in arterial P_O2 >20 mm Hg occurred in 5 of 6 cases within 30 min of commencing adenosine infusion. Individual maximal increases in PaO₂ ranged from 31 to 131 mm Hg. Three neonates survived and 3 died. Amongst deaths, intensive support was withdrawn in a preterm neonate due to severe arthrogryposis/pulmonary hypoplasia. Of the remaining 2, the improvement in oxygenation persisted until death occurred from causes unrelated to adenosine. Side effects related to adenosine (bradycardia, hypotension, prolonged bleeding time) did not occur. Due to its ease of availability, administration and extremely short half-life, adenosine may be an important therapeutic option in PPHN.

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Effect of adenosine and its analogues on calcium influx in coronary artery

Cited by 13 publications

References 0 publications

Relaxing Effects of Dilazep and Lidoflazine in Dog Cerebral and Renal Arteries Independent of Adenosine

Relaxing Effects of Dilazep and Lidoflazine in Dog Cerebral and Renal Arteries Independent of Adenosine

Differences between the Vasorelaxant Activity of Adenosine-receptor Agonists on Guinea-pig Isolated Aorta Precontracted with Noradrenaline or Phenylephrine

Improved Oxygenation following Adenosine Infusion in Persistent Pulmonary Hypertension of the Newborn

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