PRESENCE OF FUNCTIONAL TYPE-B NATRIURETIC PEPTIDE RECEPTOR IN HUMAN OCULAR CELLS

Purpose. To study the effects of natriuretic peptides on cyclic guanos ine monophosphate (cGMP) production and calcium mobilization in cultur ed human ocular cells. Methods. Cultured simian virus 40-transformed ( HTM-3) and nontransformed (HTM-16) human trabecular meshwork (TM) cell s and nontransformed human ciliary muscle (CM) cells were used. Accumu lation of cGMP in cell lysate was measured by radioimmunoassay. Intrac ellular calcium concentration was measured by microscope-based ratiofl uorometry. Results. Both atrial natriuretic peptide (ANP) and C-type n atriuretic peptide (CNP) increased the accumulation of cGMP in HTM-3, HTM-16, and CM cells. In the nontransformed TM cells, CNP was five tim es more efficacious (maximal effect of CNP was 497% +/- 44% that of AN P) and 10 times more potent than ANP (ANP, log [EC(50)] = -6.99 +/- 0. 08; CNP, log [EC(50)] = -7.96 +/- 0.20). Similar results were seen in HTM-3 and CM cells. Under the assay conditions used, the peptides incr eased only the production of cGMP without changing its degradation rat e. The peptide-induced increase of cGMP in the TM and CIM cells correl ated with suppression of carbachol-induced calcium mobilization in the cell. Conclusions. It is known that CNP, but not ANP, selectively act ivates die guanylyl cyclase associated with the type B natriuretic pep tide receptor (NPR-B). Thus, the data suggest that NPR-B is the primar y functional NPR in the TM and CM cells. The effects on cGMP and calci um produced by the activation of this receptor are expected to alter T M and CM contractility and may affect aqueous humor hydrodynamics and intraocular pressure.