October 1989
Volume 30, Issue 10
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Articles  |   October 1989
Activation of beta-adrenergic receptors causes stimulation of cyclic AMP, inhibition of inositol trisphosphate, and relaxation of bovine iris sphincter smooth muscle. Biochemical and functional interactions between the cyclic AMP and calcium signalling systems.
Author Affiliations
  • S D Tachado
    Department of Cell and Molecular Biology, Medical College of Georgia, Augusta.
  • R A Akhtar
    Department of Cell and Molecular Biology, Medical College of Georgia, Augusta.
  • A A Abdel-Latif
    Department of Cell and Molecular Biology, Medical College of Georgia, Augusta.
Investigative Ophthalmology & Visual Science October 1989, Vol.30, 2232-2239. doi:
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      S D Tachado, R A Akhtar, A A Abdel-Latif; Activation of beta-adrenergic receptors causes stimulation of cyclic AMP, inhibition of inositol trisphosphate, and relaxation of bovine iris sphincter smooth muscle. Biochemical and functional interactions between the cyclic AMP and calcium signalling systems.. Invest. Ophthalmol. Vis. Sci. 1989;30(10):2232-2239.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

We have investigated the interactions between the cAMP and inositol 1,4,5-trisphosphate (IP3)-Ca2+ signalling systems in the bovine iris sphincter by measuring the effects of beta-adrenergic and cholinergic muscarinic agonists and antagonists on cAMP formation, IP3 accumulation and muscle contraction-relaxation. (1) Addition of 5 microM isoproterenol (ISO) or forskolin (5 microM) consistently produced stimulation of cAMP (540%), inhibition of IP3 (34%) and complete relaxation of the muscle. The ISO effects were dose-dependent, with EC50 values for cAMP formation, IP3 inhibition and muscle relaxation of 2.8 X 10(-7) M, 3.4 X 10(-7) M and 0.45 X 10(-7) M, respectively. (2) Timolol, a beta-adrenergic antagonist, inhibited the ISO effects in a dose-dependent manner, with IC50 values for cAMP formation, IP3 accumulation and muscle relaxation of 1.8 X 10(-5) M, 3.2 X 10(-5) M and 2.2 X 10(-5) M, respectively. (3) The effects of ISO (0.5 microM) were time-dependent, and they clearly indicate a temporal relationship between the agonist-induced stimulation of cAMP, inhibition of IP3, and relaxation of the muscle. Within 15 sec following the addition of ISO, there was a marked increase in the level of cAMP, a decrease in IP3, and this was accompanied by an equally rapid relaxation of the muscle. (4) Addition of carbachol (CCh) to iris sphincter pretreated with ISO decreased cAMP formation and reversed muscle relaxation to complete contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

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