Natriuretic peptide receptors on human trabecular meshwork cells

Area of Science:

• Ophthalmology
• Endocrinology
• Cell Biology

Background:

• Natriuretic peptides (NPs) play roles in cardiovascular and renal physiology.
• Trabecular meshwork (TM) cells are crucial for regulating intraocular pressure.
• The presence and function of NP receptors in TM cells are not fully elucidated.

Purpose of the Study:

• To investigate the effects of different natriuretic peptides on cyclic guanosine monophosphate (cGMP) formation in human TM cells.
• To characterize natriuretic peptide binding sites on human TM cells.

Main Methods:

• Human TM cells were treated with various natriuretic peptides (CNP, BNP, ANP) to measure cGMP production.
• Radioligand binding assays using [125I]ANP were performed to identify and quantify NP receptors.

Main Results:

• C-type natriuretic peptide (CNP) significantly stimulated cGMP formation (18-25 fold) with high potency (EC50 ~20-30 nM).
• Brain natriuretic peptide (BNP) showed moderate stimulation (7 fold), while Atrial natriuretic peptide (ANP) had minimal effect at lower concentrations.
• Displacement studies indicated a single ANP binding site (Kd ~0.15 nM) and identified C-type natriuretic peptide receptors (NPR-C) as the predominant subtype.

Conclusions:

• Human TM cells possess natriuretic peptide B receptors (NPR-B) as the primary subtype linked to guanylyl cyclase activity.
• Natriuretic peptide C receptors (NPR-C) are the numerically predominant subtype on human TM cells.
• These findings suggest a potential role for natriuretic peptides in regulating TM cell function and intraocular pressure.