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. 1982 Oct;331:429–441. doi: 10.1113/jphysiol.1982.sp014380

Effects of β-adrenergic stimulation on calcium movements in rabbit aortic smooth muscle: relationship with cyclic AMP

Kaushik D Meisher 1,*, Cornelis van Breemen 1
PMCID: PMC1197757  PMID: 6296369

Abstract

1. The effects of isoprenaline (10-6 M) on relaxation, unidirectional as well as net Ca2+ fluxes, and cyclic AMP levels were investigated in rabbit aorta under the condition of high-K+ depolarization in the presence of phentolamine (10-5 M).

2. Isoprenaline (10-6 M) caused significant inhibition of Ca2+ influx stimulated by 145 mM-K+ (0 Na+) solution. The time courses of Ca2+ influx inhibition and relaxation by isoprenaline were parallel. Isoprenaline also caused a significant inhibition of high-K+-induced gain in net Ca2+ content.

3. Ro 20-1724 (1 mM), a phosphodiesterase inhibitor, also caused relaxation and Ca2+ influx inhibition in high-K+-depolarized rabbit aorta. Pre-treatment with Ro 20-1724 potentiated isoprenaline-induced Ca2+ influx inhibition and relaxation.

4. Isoprenaline and Ro 20-1724 each alone increased cyclic AMP levels. Furthermore pre-treatment with Ro 20-1724 caused potentiation of isoprenaline-induced increases in cyclic AMP levels.

5. At submaximal concentration, D600 (10-7 M) caused partial inhibition of high-K+-stimulated Ca2+ influx and produced relaxation. However, unlike Ro 20-1724, it did not potentiate isoprenaline-induced Ca2+ influx inhibition and relaxation. D600 does not increase cyclic AMP levels in smooth muscle.

6. Dibutyryl cyclic AMP (1 mM), a lipid-soluble analogue of cyclic AMP, caused relaxation and inhibited high-K+-stimulated Ca2+ influx.

7. Isoprenaline failed to cause stimulation of Ca2+ efflux in high-K+-depolarized rabbit aorta.

8. It is concluded that the inhibition of Ca2+ influx may be one of the mechanisms by which β-receptor stimulation can reduce intracellular free Ca2+ to promote relaxation of smooth muscle. The data support the involvement of cyclic AMP in this action of the β-agonist.

9. Since the experiments were conducted in 145 mM-K+ (0 Na+) depolarizing conditions, the role of hyperpolarization or of a Na+—Ca2+ exchange mechanism in isoprenaline-induced Ca2+ influx inhibition and/or relaxation can be excluded.

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Selected References

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