Effects of Catecholamines and their Metabolites and other Pharmacological Agents on Arachidonic Acid Metabolism and Prostaglandin Release by Rabbit Iris Muscle and Iris Microsomes

  • Ata A. Abdel-Latif
  • Jack P. Smith
  • Sardar Y. K. Yousufzai
  • Richard K. Dover
Chapter
Part of the Experimental and Clinical Neuroscience book series (ECN)

Summary

Comparative studies were conducted on the effects of catecholamines and their metabolites and other pharmacological agents on arachidonic acid (AA) metabolism and prostaglandin (PG) release by rabbit iris smooth muscle and iris microsomes. Norepinephrine (Nor) and related compounds were found to stimulate significantly the conversion of l-14C-AA into PGF2and PGE2. Nor also stimulated the basal release of PGE2 from the iris in a dose dependent manner. The Nor-stlimitation of PG synthesis was blocked by indomethacin (1.5 μM). The studies on the mechanism(s) underlying the action of catecholamines on PG synthesis revealed the following: (1) The structural requirement for maximal catecholamine stimulation of PG synthesis by the iris and iris microsomes is a catechol nucleus and ethylamine polar side-chain. Thus the deaminated metabolites of Nor had little effect on PG synthesis by the iris and iris microsomes; in contrast normetanephrine stimulated significantly PG synthesis. Furthermore, catechol inhibited PG synthesis by the iris in a dose-dependent manner. (2) In order for the amine to activate PG synthesis by the iris,the amine should be permeable to the cell membrane. Permeability studies revealed that 14C-Nor is taken up rapidly by the iris. (3) α-Adrenergic agonists stimulated PG synthesis and release by the iris, and this was blocked by phentolamine

It is concluded that in the iris, catecholamines stimulate PG synthesis in two ways: (a) They are taken up by the tissue where act as cofactors for the cyclo-oxygenation of AA. (b) They stimulate PG synthesis through adrenoreceptor-mediated mechanisms. Participation of an adrenoreceptor-linked phosphoLipase A2 in the expression of the catechoLamine stimulation of PG synthesis remains to be defined.

Keywords

Basal Release Arachidonic Acid Release PGE2 Synthesis Prostaglandin Biosynthesis Rabbit Iris 
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Copyright information

© The Humana Press Inc. 1983

Authors and Affiliations

  • Ata A. Abdel-Latif
    • 1
  • Jack P. Smith
    • 1
  • Sardar Y. K. Yousufzai
    • 1
  • Richard K. Dover
    • 1
  1. 1.Department of Cell and Molecular BiologyMedical College of GeorgiaAugustaUSA

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