The calcium-related basis of action of adenosine in rabbit aortic smooth muscle

Zawadzki, John V.; Weiss, George B.

doi:10.1016/0306-3623(90)91015-j

Cited by 4 publications

(4 citation statements)

References 11 publications

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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: 92%

“…Adenosine also reduced both noradrenaline-and phenylephrine-induced tone in a concentrationdependent manner. The mechanism of vasorelaxation by adenosine has been attributed to both extracellular and intracellular sites (Collis & Brown 1983;Young & Merrill 1983;Long & Stone 1987;Zawadzki & Weiss 1990), the extracellular site being the A 2B -receptor (Martin 1992). Adenosine was consistently a more effective relaxant than NECA, suggesting that adenosine has an additional action, presumably at the intracellular site.…”

Section: Cumulative Concentration±response Curvesmentioning

confidence: 99%

“…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).…”

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confidence: 99%

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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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Section: Effects Of Neca On Contractions Dependent Upon Extracellularmentioning

confidence: 92%

Section: Cumulative Concentration±response Curvesmentioning

confidence: 99%

mentioning

confidence: 99%

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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

View full text Add to dashboard Cite

show abstract

“…These conflicting results again show the varying effects of CGS 21680 in different vascular tissues, possibly due to activation of different receptor subtypes. Other mechanisms besides those that involve adenylate cyclase that might be mediating the relaxant effects of CGS 21680 and NECA could include an adenosineinduced membrane hyperpolarization (139), an inhibition of phospholipase C (90), or a decrease in Ca2 + influx into vascular smooth muscle (1 13,138).…”

Section: Signal Transduction Mechanismsmentioning

confidence: 99%