Inhibition of NHE-1 Na+/H+ exchanger by natriuretic peptides in ocular nonpigmented ciliary epithelium.
The natriuretic peptides (NPs) atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) display hypotensive effects in the mammalian eye by lowering the intraocular pressure (IOP), a function that is mediated by the bilayer ocular ciliary epithelium (CE), in conjunction with the trabecular meshwork. ANP regulates Na(+)/H(+) exchanger (NHE) activity, and inhibitors of NHE have been shown to lower IOP. We examined whether NPs influence the NHE activity of the CE, which is comprised of pigmented (PE) and nonpigmented (NPE) epithelial cells, by directly recording the rate of intracellular pH (pH(i)) recovery from its inner NPE cell layer. NPs inhibited, in a dose-dependent manner (1-100 nM), the rate of pH(i) recovery with the order of potency CNP > ANP > BNP, indicative that this inhibition is mediated by the presence of NPR type B receptors. 8-Bromo-cGMP (8-BrcGMP), a nonhydrolyzable analog of cGMP, mimicked NPs in inhibiting the rate of Na(+)-dependent pH(i) recovery. In contrast, ethylisopropyl amiloride (EIPA, 100 nM) or amiloride (10 microM) completely abolished the pH(i) recovery by NHE. 18alpha-Glycyrrhetinic acid (18alpha-GA), a gap junction blocker, attenuated the inhibitory effect of CNP on the rate of pH(i) recovery, suggesting that NHE activity in both cell layers of the CE is coregulated. This interpretation was supported, in part, by the coexpression of NHE-1 isoform mRNA in both NPE and PE cells. The mechanism by which the inhibitory effect of NPs on NHE-1 activity might influence the net solute movement or fluid transport by the bilayer CE remains to be determined.
Fidzinski
Pawel
P
Dept. of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT 06510, USA.
Salvador-Silva
Mercedes
M
Choritz
Lars
L
Geibel
John
J
Coca-Prados
Miguel
M
D000818:Animals; D001082:Aqueous Humor / Q000737:chemistry / Q000378:metabolism*; D002417:Cattle; D002924:Ciliary Body / Q000187:drug effects / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006863:Hydrogen-Ion Concentration; D007429:Intraocular Pressure / Q000502:physiology; D045265:Natriuretic Peptides / Q000494:pharmacology*; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000502:physiology*; D020033:Protein Isoforms / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017923:Sodium-Hydrogen Exchangers / Q000187:drug effects / Q000378:metabolism*
D045265:Natriuretic Peptides; D020033:Protein Isoforms; D017923:Sodium-Hydrogen Exchangers; C069139:growth factor-activatable Na-H exchanger NHE-1