Inhibitory modulation by cAMP of isoproterenol-induced prostacyclin synthesis in rabbit heart

J. L. Williams, Kafait Malik

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6 Citations (Scopus)

Abstract

β-Adrenergic receptor activation in heart is associated with enhanced production of adenosine 3',5'-cyclic monophosphate (cAMP) and prostaglandins (PG). The purpose of the present study was to test the hypothesis that cAMP mediates or modulates PG synthesis elicited by activation of β-adrenergic receptors in the isolated, perfused rabbit heart. Infusion of 8-(4-chlorophenylthio)(cpt)-cAMP (100 μM), an analogue of cAMP, or stimulation of endogenous cAMP generation with forskolin (2 μM) resulted in a reduction of perfusion pressure and an increase in heart rate and contractility but had no effect on 6-keto-PGF(1α) output. 6-Keto-PGF(1α) production elicited by a bolus injection of isoproterenol (Isop) (475 pmol), however, was reduced by > 50% in the presence of these agents. cpt-cAMP was also found to inhibit 6-keto-PGF(1α) output elicited by the calcium ionophore A23187 but not that in response to exogenous arachidonic acid. Perfusion with the adenosine analogue adenylate cyclase inhibitor PIA (1 μM) enhanced by twofold Isop-stimulated output of 6-keto-PGF(1α), whereas cAMP accumulation was prevented. Isop-stimulated production of 6-keto-PGF(1α) was inhibited by 50% in the presence of the phosphodiesterase inhibitors 1-methyl-3-isobutylxanthine (50 μM), Ro 20-1724 (300 μM), or cilostamide (5 μM), whereas both basal and Isop-stimulated cAMP accumulations were enhanced by these agents. These data suggest that cAMP acts as an inhibitory modulator of PG synthesis in response to β-adrenergic receptor activation in rabbit heart.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume257
Issue number4
StatePublished - Jan 1 1989

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Prostaglandins F
Epoprostenol
Isoproterenol
Rabbits
Adrenergic Receptors
Prostaglandins
4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone
Perfusion
Myocardial Contraction
1-Methyl-3-isobutylxanthine
Phosphodiesterase Inhibitors
Calcium Ionophores
Calcimycin
Colforsin
Arachidonic Acid
Cyclic AMP
Adenosine
Heart Rate
Pressure
Injections

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Cite this

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title = "Inhibitory modulation by cAMP of isoproterenol-induced prostacyclin synthesis in rabbit heart",
abstract = "β-Adrenergic receptor activation in heart is associated with enhanced production of adenosine 3',5'-cyclic monophosphate (cAMP) and prostaglandins (PG). The purpose of the present study was to test the hypothesis that cAMP mediates or modulates PG synthesis elicited by activation of β-adrenergic receptors in the isolated, perfused rabbit heart. Infusion of 8-(4-chlorophenylthio)(cpt)-cAMP (100 μM), an analogue of cAMP, or stimulation of endogenous cAMP generation with forskolin (2 μM) resulted in a reduction of perfusion pressure and an increase in heart rate and contractility but had no effect on 6-keto-PGF(1α) output. 6-Keto-PGF(1α) production elicited by a bolus injection of isoproterenol (Isop) (475 pmol), however, was reduced by > 50{\%} in the presence of these agents. cpt-cAMP was also found to inhibit 6-keto-PGF(1α) output elicited by the calcium ionophore A23187 but not that in response to exogenous arachidonic acid. Perfusion with the adenosine analogue adenylate cyclase inhibitor PIA (1 μM) enhanced by twofold Isop-stimulated output of 6-keto-PGF(1α), whereas cAMP accumulation was prevented. Isop-stimulated production of 6-keto-PGF(1α) was inhibited by 50{\%} in the presence of the phosphodiesterase inhibitors 1-methyl-3-isobutylxanthine (50 μM), Ro 20-1724 (300 μM), or cilostamide (5 μM), whereas both basal and Isop-stimulated cAMP accumulations were enhanced by these agents. These data suggest that cAMP acts as an inhibitory modulator of PG synthesis in response to β-adrenergic receptor activation in rabbit heart.",
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AU - Williams, J. L.

AU - Malik, Kafait

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N2 - β-Adrenergic receptor activation in heart is associated with enhanced production of adenosine 3',5'-cyclic monophosphate (cAMP) and prostaglandins (PG). The purpose of the present study was to test the hypothesis that cAMP mediates or modulates PG synthesis elicited by activation of β-adrenergic receptors in the isolated, perfused rabbit heart. Infusion of 8-(4-chlorophenylthio)(cpt)-cAMP (100 μM), an analogue of cAMP, or stimulation of endogenous cAMP generation with forskolin (2 μM) resulted in a reduction of perfusion pressure and an increase in heart rate and contractility but had no effect on 6-keto-PGF(1α) output. 6-Keto-PGF(1α) production elicited by a bolus injection of isoproterenol (Isop) (475 pmol), however, was reduced by > 50% in the presence of these agents. cpt-cAMP was also found to inhibit 6-keto-PGF(1α) output elicited by the calcium ionophore A23187 but not that in response to exogenous arachidonic acid. Perfusion with the adenosine analogue adenylate cyclase inhibitor PIA (1 μM) enhanced by twofold Isop-stimulated output of 6-keto-PGF(1α), whereas cAMP accumulation was prevented. Isop-stimulated production of 6-keto-PGF(1α) was inhibited by 50% in the presence of the phosphodiesterase inhibitors 1-methyl-3-isobutylxanthine (50 μM), Ro 20-1724 (300 μM), or cilostamide (5 μM), whereas both basal and Isop-stimulated cAMP accumulations were enhanced by these agents. These data suggest that cAMP acts as an inhibitory modulator of PG synthesis in response to β-adrenergic receptor activation in rabbit heart.

AB - β-Adrenergic receptor activation in heart is associated with enhanced production of adenosine 3',5'-cyclic monophosphate (cAMP) and prostaglandins (PG). The purpose of the present study was to test the hypothesis that cAMP mediates or modulates PG synthesis elicited by activation of β-adrenergic receptors in the isolated, perfused rabbit heart. Infusion of 8-(4-chlorophenylthio)(cpt)-cAMP (100 μM), an analogue of cAMP, or stimulation of endogenous cAMP generation with forskolin (2 μM) resulted in a reduction of perfusion pressure and an increase in heart rate and contractility but had no effect on 6-keto-PGF(1α) output. 6-Keto-PGF(1α) production elicited by a bolus injection of isoproterenol (Isop) (475 pmol), however, was reduced by > 50% in the presence of these agents. cpt-cAMP was also found to inhibit 6-keto-PGF(1α) output elicited by the calcium ionophore A23187 but not that in response to exogenous arachidonic acid. Perfusion with the adenosine analogue adenylate cyclase inhibitor PIA (1 μM) enhanced by twofold Isop-stimulated output of 6-keto-PGF(1α), whereas cAMP accumulation was prevented. Isop-stimulated production of 6-keto-PGF(1α) was inhibited by 50% in the presence of the phosphodiesterase inhibitors 1-methyl-3-isobutylxanthine (50 μM), Ro 20-1724 (300 μM), or cilostamide (5 μM), whereas both basal and Isop-stimulated cAMP accumulations were enhanced by these agents. These data suggest that cAMP acts as an inhibitory modulator of PG synthesis in response to β-adrenergic receptor activation in rabbit heart.

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