Prostaglandin E2 synthesis elicited by adrenergic stimuli in guinea pig trachea is mediated primarily via activation of β2 adrenergic receptors

D. B. Lew, G. L. Nadel, Kafait Malik

Research output: Contribution to journalArticle

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Abstract

Prostaglandin (PG) E2 synthesis elicited by adrenergic agonists in the guinea pig trachea has been shown to be mediated via activation of β-adrenergic receptors. The purpose of this study was to examine arachidonic acid (AA) metabolism and to characterize the subtype of β receptor involved in PG synthesis. [14C]AA was incubated with guinea pig tracheal rings, and the radiolabelled products were extracted from the medium. Thin layer chromatographic analysis and radioimmunoassay of the extract showed that [14C]AA was incorporated into guinea pig tracheal rings and metabolized mainly into radiolabeled and immunoreactive PGE2 (iPGE2) and smaller amounts into PGF. Trace amounts of PGD2, TxB2 and 6-keto-PGF but not LTB4 or LTC4 were detected by enzyme immunoassay. Incubation of guinea pig tracheal rings for 10 min with isoproterenol or salbutamol resulted in a significant increase in PGE2 synthesis (optimum concentration 0.1 μM for both compounds). In contrast, dobutamine, BRL 37344, BRL 28410, norepinephrine, phenylephrine, and xylazine (up to 1 μM) did not significantly increase PGE2 production. Isoproterenol-induced iPGE2 production was inhibited by the selective β2 receptor antagonist butoxamine (0.1-1.0 μM) and somewhat reduced by the β1 receptor antagonist practolol (1 μM). The increase in PGE2 synthesis was diminished with increasing concentrations of isoproterenol (0.5-5.0 μM) or salbutamol (0.5-1.0 μM); but it was reversed by pretreatment of tracheal rings with the protein synthesis inhibitors cycloheximide (0.9 μM) and actinomycin D (2 μM) but not by phenylisopropyl adenosine (0.1-1.0 μM), an inhibitor of adenylyl cyclase. These data suggest that isoproterenol-induced iPGE2 synthesis is primarily via activation of a β2 adrenergic receptor. Failure to enhance iPGE2 synthesis by a high concentration of isoproterenol is likely to be due to an induction of new inhibitory protein synthesis.

Original languageEnglish (US)
Pages (from-to)399-412
Number of pages14
JournalProstaglandins
Volume44
Issue number5
DOIs
StatePublished - Jan 1 1992

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Trachea
Dinoprostone
Adrenergic Agents
Adrenergic Receptors
Guinea Pigs
Chemical activation
Isoproterenol
Arachidonic Acid
Albuterol
Butoxamine
Practolol
Xylazine
Prostaglandin D2
Thin layer chromatography
Leukotriene C4
Adrenergic Agonists
Protein Synthesis Inhibitors
Dinoprost
Leukotriene B4
Dobutamine

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Endocrinology

Cite this

Prostaglandin E2 synthesis elicited by adrenergic stimuli in guinea pig trachea is mediated primarily via activation of β2 adrenergic receptors. / Lew, D. B.; Nadel, G. L.; Malik, Kafait.

In: Prostaglandins, Vol. 44, No. 5, 01.01.1992, p. 399-412.

Research output: Contribution to journalArticle

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