Alpha₁-Adrenoceptors in the Albino Rabbit Ciliary Process

Abstract

H-Prazosin and^H-rauwolscine binding sites were identified in a membrane suspension prepared from albino rabbit iris + ciliary body. Scatchard analysis of saturation binding experiments demonstrated that both %-prazosin and %-rauwolscine bind to a single population of binding sites with Krj values of 0.87 nM and 5.33 nM, respectively. Bmax values of 65.7 and 198 fmol/mg protein were obtained for^H -prazosin and 3jj-rauwolscine, respectively. Displacement studies by several adrenergic agonists and antagonists indicated that^H -prazosin and^H-rauwolscine labelled a^-and o^-adrenoceptors, respectively, in the iris + ciliary body. Epinephrine, norepinephrine and phenylephrine were able to stimulate the synthesis of 3H-inosit.0l. phosphates in ciliary processes labelled with 3H-inositol, with EC50 values of 2.4, 12 and 10 yM, respectively. The corresponding maximum stimulations of basal activity were 433, 430 and 283%, respectively. Phenylephrine behaved like a partial agonist in this assay. The norepinephrine response could be potently antagonized by prazosin (K^= 27 nM), with rauwolscine being 285-fold less potent. An epithelial cell suspension was prepared from the ciliary process. Stimulation of phosphatidylinositol turnover by norepinephrine (0.1 mM) was observed, and this could be blocked by prazosin (10 \M), thus, indicating the presence of oci-adrenoceptors, coupled to phosphatidylinositol turnover, in epithelial cells of the rabbit ciliary process.

Adrenergic-melatonin heteroreceptor complexes are key in controlling ion homeostasis and intraocular eye pressure and their disruption contributes to hypertensive glaucoma

“…Together, our findings provide a better understanding of the ciliary body physiology, completing a preclinical translational research addressed to combat glaucoma. Remarkably, a therapeutic strategy resulting from combining melatonin, sold as a supplement and lacking collateral effects even at high doses in the eye (Rosenstein et al, 2010;Sanchez-Barcelo, Mediavilla, Tan, & Reiter, 2010), and prazosin, approved for the therapy of blood hypertension (Brogden et al, 1977;Mallorga, Buisson, & Sugrue, 1988;Singleton et al, 1989;Torvik & Madsbu, 1986), could readily enter into clinical trials to assay for safety and efficacy in humans.…”

Adreno–melatonin receptor complexes control ion homeostasis and intraocular pressure ‐ their disruption contributes to hypertensive glaucoma

“…Together, our findings provide a better understanding of the ciliary body physiology, completing a preclinical translational research addressed to combat glaucoma. Remarkably, a therapeutic strategy resulting from combining melatonin, sold as a supplement and lacking collateral effects even at high doses in the eye (Rosenstein et al, ; Sánchez‐Barceló, Mediavilla, Tan, & Reiter, ), and prazosin, approved for the therapy of blood hypertension (Brogden et al, ; Mallorga, Buisson, & Sugrue, ; Singleton et al, ; Torvik & Madsbu, ), could readily enter into clinical trials to assay for safety and efficacy in humans with ocular hypertension.…”

Adrenergic regulation of calcium‐activated potassium current in cultured rabbit pigmented ciliary epithelial cells

“…A number of closely related subtypes of the α 1 subfamily (α 1A , α 1B , α 1C and α 1D ) and the α 2 subfamily (α 2A/D , α 2B and α 2C ) have been identified on the basis of their sequence homology, pharmacological profile and signal transduction mechanisms (Watson & Arkinstall, 1994; MacKinnon et al 1994). Both subfamilies of α‐AR have been identified on the rabbit CBE (Mallorga et al 1988; Jin et al 1994) and more recent studies have suggested that in rabbit CBE α 1 ‐ARs are localized on the PCE cells, whilst α 2 ‐ARs, specifically α 2A ‐ARs, are localized to the NPE cells (Schutte et al 1996; Suzuki et al 1997). Our studies are consistent with these findings in that the phenylephrine‐mediated increase in I K(Ca) is mediated via an α 1 ‐receptor subtype in rabbit PCE cells.…”