Presence of functional type B natriuretic peptide receptor in human ocular cells.
OBJECTIVE
To study the effects of natriuretic peptides on cyclic guanosine monophosphate (cGMP) production and calcium mobilization in cultured human ocular cells.


METHODS
Cultured simian virus 40-transformed (HTM-3) and nontransformed (HTM-16) human trabecular meshwork (TM) cells and nontransformed human ciliary muscle (CM) cells were used. Accumulation of cGMP in cells lysate was measured by radioimmunoassay. Intracellular calcium concentration was measured by microscope-based ratiofluorometry.


RESULTS
Both atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) increased the accumulation of cGMP in HTM-3, HTM-16, and CM cells. In the nontransformed TM cells, CNP was five times more efficacious (maximal effect of CNP was 497% +/- 44% that of ANP) and 10 times more potent than ANP (ANP, log [EC50] = -6.99 +/- 0.08; CNP, log [EC50] = -7.96 +/- 0.20). Similar results were seen in HTM-3 and CM cells. Under the assay conditions used, the peptides increased only the production of cGMP without changing its degradation rate. The peptide-induced increase of cGMP in the TM and CM cells correlated with suppression of carbachol-induced calcium mobilization in the cell.


CONCLUSIONS
It is known that CNP, but not ANP, selectively activates the guanylyl cyclase associated with the type B natriuretic peptide receptor (NPR-B). Thus, the data suggest that NPR-B is the primary functional NPR in the TM and CM cells. The effects on cGMP and calcium produced by the activation of this receptor are expected to alter TM and CM contractility and may affect aqueous humor hydrodynamics and intraocular pressure.
Pang
I H
IH
Alcon Laboratories, University of North Texas Health Science Center, Fort Worth, USA.
Shade
D L
DL
Matsumoto
S
S
Steely
H T
HT
DeSantis
L
L
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002924:Ciliary Body / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006152:Cyclic GMP / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007429:Intraocular Pressure; D007700:Kinetics; D009119:Muscle Contraction; D020098:Natriuretic Peptide, C-Type; D011506:Proteins / Q000494:pharmacology*; D017461:Receptors, Atrial Natriuretic Factor / Q000187:drug effects / Q000502:physiology*; D013539:Simian virus 40; D014129:Trabecular Meshwork / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D011506:Proteins; D020098:Natriuretic Peptide, C-Type; D009320:Atrial Natriuretic Factor; D002217:Carbachol; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C073616:atrial natriuretic factor receptor C; D006152:Cyclic GMP; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine