Prostaglandin E2 synthesis elicited by adrenergic stimuli in guinea pig trachea is mediated primarily via activation of beta 2 adrenergic receptors

Prostaglandins. 1992 Nov;44(5):399-412. doi: 10.1016/0090-6980(92)90136-h.

Abstract

Prostaglandin (PG) E2 synthesis elicited by adrenergic agonists in the guinea pig trachea has been shown to be mediated via activation of beta-adrenergic receptors. The purpose of this study was to examine arachidonic acid (AA) metabolism and to characterize the subtype of beta 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 PGF2 alpha. Trace amounts of PGD2, TxB2 and 6-keto-PGF1 alpha 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 microM for both compounds). In contrast, dobutamine, BRL 37344, BRL 28410, norepinephrine, phenylephrine, and xylazine (up to 1 microM) did not significantly increase PGE2 production. Isoproterenol-induced iPGE2 production was inhibited by the selective beta 2 receptor antagonist butoxamine (0.1-1.0 microM) and somewhat reduced by the beta 1 receptor antagonist practolol (1 microM). The increase in PGE2 synthesis was diminished with increasing concentrations of isoproterenol (0.5-5.0 microM) or salbutamol (0.5-1.0 microM); but it was reversed by pretreatment of tracheal rings with the protein synthesis inhibitors cycloheximide (0.9 microM) and actinomycin D (2 microM) but not by phenylisopropyl adenosine (0.1-1.0 microM), an inhibitor of adenylyl cyclase. These data suggest that isoproterenol-induced iPGE2 synthesis is primarily via activation of a beta 2 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Albuterol / pharmacology
  • Animals
  • Arachidonic Acid / metabolism
  • Butoxamine / pharmacology
  • Colforsin / pharmacology
  • Cyclic AMP / physiology
  • Cycloheximide / pharmacology
  • Dactinomycin / pharmacology
  • Dinoprostone / biosynthesis*
  • Dobutamine / pharmacology
  • Guinea Pigs
  • In Vitro Techniques
  • Isoproterenol / pharmacology
  • Male
  • Practolol / pharmacology
  • Receptors, Adrenergic, beta / physiology*
  • Time Factors
  • Trachea / physiology*

Substances

  • Receptors, Adrenergic, beta
  • Butoxamine
  • Dactinomycin
  • Colforsin
  • Arachidonic Acid
  • Dobutamine
  • Cycloheximide
  • Cyclic AMP
  • Dinoprostone
  • Isoproterenol
  • Albuterol
  • Practolol