title: Hyperosmolality rapidly reduces atrial-natriuretic-peptide-dependent cyclic guanosine monophosphate production in cultured rat inner medullary collecting duct cells.
abstract: The present study was undertaken to explore the acute effect of hyperosmolality on the response of cultured rat inner medullary collecting duct (IMCD) cells to atrial natriuretic peptide (ANP). In contrast to the stimulatory effect of chronic incubation (12 h) in hypertonic medium, it was found that short-term incubation (< 2 h) reversibly suppressed the ANP-dependent cyclic guanosine monophosphate (cGMP) production. Urea, NaCl and mannitol were equi-potent as the osmolyte in suppressing the ANP-dependent cGMP production. Receptor binding assay revealed that hyperosmolality induced a rapid and marked reduction of the maximum binding (Bmax) of ANP without a significant change of the dissociation constant (Kd). Pretreatment with protein kinase C inhibitors (calphostin-C, staurosporin) or with cytoskeleton modulators (cytochalasin-B, colchicine) did not affect the inhibitory effect of hyperosmolality. In conclusion, acute hypertonicity inhibited the ANP-induced cGMP production in contrast to chronic hypertonicity, and reduction of the number of ANP binding sites was considered to be a mechanism responsible for the inhibitory effect of hypertonicity.
authors.affiliation: Division of Nephrology, Jichi Medical School, Tochigi, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Iimura
authors.forename: E
authors.initials: E
authors.lastname: Kusano
authors.forename: F
authors.initials: F
authors.lastname: Ishida
authors.forename: S
authors.initials: S
authors.lastname: Oono
authors.forename: Y
authors.initials: Y
authors.lastname: Ando
authors.forename: Y
authors.initials: Y
authors.lastname: Asano
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism*; D003571:Cytochalasin B / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009994:Osmolar Concentration; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology; D019311:Staurosporine; D014508:Urea / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D004791:Enzyme Inhibitors; D009281:Naphthalenes; C061465:calphostin complex; D003571:Cytochalasin B; D008353:Mannitol; D012965:Sodium Chloride; D009320:Atrial Natriuretic Factor; D014508:Urea; D011493:Protein Kinase C; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP; D019311:Staurosporine; D003078:Colchicine