Distribution and properties of β-adrenergic receptors in human iris-ciliary body

M. B. Wax, P. B. Molinoff

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

β-Adrenergic receptors from the iris-ciliary body of human eyes removed shortly after death were studied using membranes prepared by isopycnic centrifugation of tissue homogenates. This procedure separates uveal melanin pigment from plasma membranes and reduces nonspecific binding of 125I-iodopindolol. The observed binding of 125I-iodopindolol was of high affinity (K(d) = 78 ± 6.6 pM), saturable, and fully reversible (t( 1/2 ) = 4.6 min). Scatchard plots were linear and revealed a B(max) of 134 ± 20 fmol/mg of protein from the whole iris-ciliary body. The affinities of the receptors for a series of agonists and antagonists were determined. The order of potency for the inhibition of the binding of the radioligand by antagonists was ICI 118,551 > MK950 > propranolol > ICI 89,406 > metoprolol. This order of potency is characteristic of β-adrenergic receptors of the β2 subtype. Preparations of iris-ciliary body were also subjected to microdissection prior to density gradient centrifugation to permit the study of β-adrenergic receptors in the ciliary processes, ciliary body, and iris. Each of these regions was found to contain approximately one third of the total number of β-adrenergic receptors in the human iris-ciliary body. The highest density of receptors was located in the ciliary processes (180 ± 40 fmol/mg of protein), while the density of receptors in the iris (98 ± 7.5 fmol/mg of protein) and ciliary body (less the processes ) (42 ± 17 fmol/mg of protein) was notably lower. Only β2-adrenergic receptors are detectable by competition experiments in the iris-ciliary body as a whole, or in the individual preparations of iris, ciliary processes, or ciliary body; however, microdissection and analysis of β-adrenergic receptor subtypes in isolated ciliary muscle permitted detection of a small number of β1-adrenergic receptors. β1-Adrenergic receptors comprised about 10% of the total number of β-adrenergic receptors in the whole iris-ciliary body. The finding that most of the β-adrenergic receptors in the human iris-ciliary body are of the β2 subtype may be of significant therapeutic importance in the medical management of glaucoma.

Original languageEnglish (US)
Pages (from-to)420-430
Number of pages11
JournalInvestigative Ophthalmology and Visual Science
Volume28
Issue number3
StatePublished - Jan 1 1987

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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