دورية أكاديمية
Renal effects of uroguanylin and guanylin in vivo.
| العنوان: | Renal effects of uroguanylin and guanylin in vivo. |
|---|---|
| المؤلفون: | Carrithers SL; Department of Internal Medicine, Division of Infectious Diseases, VA Medical Center, University of Kentucky, Lexington, KY 40536-0084, USA., Hill MJ, Johnson BR, O'Hara SM, Jackson BA, Ott CE, Lorenz J, Mann EA, Giannella RA, Forte LR, Greenberg RN |
| المصدر: | Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas [Braz J Med Biol Res] 1999 Nov; Vol. 32 (11), pp. 1337-44. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Associação Brasileira de Divulgação Científica Country of Publication: Brazil NLM ID: 8112917 Publication Model: Print Cited Medium: Print ISSN: 0100-879X (Print) Linking ISSN: 0100879X NLM ISO Abbreviation: Braz J Med Biol Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [SP, Brasil : Associação Brasileira de Divulgação Científica, 1981- |
| مواضيع طبية MeSH: | Gastrointestinal Hormones*, Enzyme Activators/*pharmacology , Kidney/*drug effects , Peptides/*pharmacology, Animals ; Animals, Newborn ; Cells, Cultured ; Cyclic GMP/metabolism ; Dose-Response Relationship, Drug ; Guanylate Cyclase/metabolism ; Intestinal Mucosa/metabolism ; Intestines/drug effects ; Kidney/physiology ; Male ; Mice ; Mice, Inbred ICR ; Mice, Knockout ; Natriuresis/drug effects ; Natriuretic Peptides ; Peptides/physiology ; RNA, Messenger/metabolism ; Receptors, Enterotoxin ; Receptors, Guanylate Cyclase-Coupled ; Receptors, Peptide/metabolism ; Urine |
| مستخلص: | Uroguanylin and guanylin are newly discovered endogenous heat-stable peptides that bind to and activate a membrane bound guanylyl cyclase signaling receptor (termed guanylyl cyclase C; GC-C). These peptides are not only found in blood but are secreted into the lumen of the intestine and effect a net secretion of electrolytes (Na+, K+, Cl-, HCO3-) and fluid into the intestine via a cyclic guanosine-3', 5'-monophosphate (cGMP) mechanism. GC-C is also the receptor for Escherichia coli heat-stable enterotoxin (STa) and activation by STa results in a diarrheal illness. Employing mouse renal in vivo models, we have demonstrated that uroguanylin, guanylin, and STa elicit natriuretic, kaliuretic, and diuretic effects. These biological responses are time- and dose-dependent. Maximum natriuretic and kaliuretic effects are observed within 30-40 min following infusion with pharmacological doses of the peptides in a sealed-urethra mouse model. Our mouse renal clearance model confirms these results and shows significant natriuresis following a constant infusion of uroguanylin for 30 min, while the glomerular filtration rate, plasma creatinine, urine osmolality, heart rate, and blood pressure remain constant. These data suggest the peptides act through tubular transport mechanisms. Consistent with a tubular mechanism, messenger RNA-differential display PCR of kidney RNA extracted from vehicle- and uroguanylin-treated mice show the message for the Na+/K+ ATPase gamma-subunit is down-regulated. Interestingly, GC-C knockout mice (Gucy2c -/-) also exhibit significant uroguanylin-induced natriuresis and kaliuresis in vivo, suggesting the presence of an alternate receptor signaling mechanism in the kidney. Thus, uroguanylin and guanylin seem to serve as intestinal and renal natriuretic peptide-hormones influencing salt and water transport in the kidney through GC-C dependent and independent pathways. Furthermore, our recent clinical probe study has revealed a 70-fold increase in levels of urinary uroguanylin in patients with congestive heart failure. In conclusion, our studies support the concept that uroguanylin and guanylin are endogenous effector peptides involved in regulating body salt and water homeostasis. |
| المشرفين على المادة: | 0 (Enzyme Activators) 0 (Gastrointestinal Hormones) 0 (Natriuretic Peptides) 0 (Peptides) 0 (RNA, Messenger) 0 (Receptors, Peptide) 140653-38-9 (guanylin) 152175-68-3 (uroguanylin) EC 4.6.1.2 (Guanylate Cyclase) EC 4.6.1.2 (Gucy2c protein, mouse) EC 4.6.1.2 (Receptors, Enterotoxin) EC 4.6.1.2 (Receptors, Guanylate Cyclase-Coupled) H2D2X058MU (Cyclic GMP) |
| تواريخ الأحداث: | Date Created: 19991124 Date Completed: 20000201 Latest Revision: 20190516 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1590/s0100-879x1999001100003 |
| PMID: | 10559834 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 0100-879X |
|---|---|
| DOI: | 10.1590/s0100-879x1999001100003 |