| Cellular signaling by cyclosporine A in contractile cells: interactions with atrial natriuretic peptide. | |
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MedLine Citation:
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PMID: 8461628 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Immunosuppressive therapy with cyclosporine A (CyA) may be associated with severe side effects such as nephrotoxicity and arterial hypertension. The partial reversibility of these effects suggests that they are at least in part functional. The present study examined the effects of CyA on cellular signaling in vascular smooth muscle cells and in glomerular mesangial cells and the interactions with the endogenous vasodilator atrial natriuretic peptide (ANP). Intracellular free calcium concentrations ([Ca2+]i) were measured using Fura-2. 45Ca2+ was used to measure Ca2+ efflux and cellular Ca2+ influx. In the presence of cyclosporine (10 micrograms/ml), the Ca(2+)-mobilizing effects of angiotensin II (10(-8)M) in smooth muscle cells and of arginine vasopressin (AVP) in mesangial cells were significantly enhanced. CyA significantly stimulated cellular Ca2+ uptake in both cell types. ANP blocked the Ca2+ mobilization by angiotensin II and AVP and also completely inhibited the potentiating effect of CyA on angiotensin II- and AVP-induced Ca2+ mobilization. ANP also completely blocked the CyA-stimulated Ca2+ uptake. These findings suggest that CyA stimulates transmembrane Ca2+ influx, thereby increasing vasopressor-sensitive intracellular Ca2+ stores and augmenting vasopressor-induced Ca2+ mobilization. This cellular effect of CyA in vitro was markedly diminished by ANP. The effects of CyA on intracellular signaling may directly enhance the contractile response of smooth muscle and the glomerular mesangium to vasopressor stimuli and may also contribute to other disturbances of cell metabolism associated with CyA. |
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Authors:
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H Meyer-Lehnert; D Bokemeyer; U Friedrichs; S Drechsler; H J Kramer |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Clinical investigator Volume: 71 ISSN: 0941-0198 ISO Abbreviation: Clin Investig Publication Date: 1993 Feb |
Date Detail:
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Created Date: 1993-05-04 Completed Date: 1993-05-04 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9207154 Medline TA: Clin Investig Country: GERMANY |
Other Details:
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Languages: eng Pagination: 153-60 Citation Subset: IM |
Affiliation:
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Medizinische Poliklinik, Universität Bonn. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin II
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pharmacology Animals Arginine Vasopressin / pharmacology Atrial Natriuretic Factor / pharmacology* Calcium / metabolism Cells, Cultured Cyclosporine / antagonists & inhibitors, pharmacology* Glomerular Mesangium / cytology, drug effects*, metabolism Male Muscle Contraction / drug effects Muscle, Smooth, Vascular / cytology, drug effects*, metabolism Rats Rats, Sprague-Dawley Signal Transduction / drug effects* |
| Chemical | |
Reg. No./Substance:
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11128-99-7/Angiotensin II; 113-79-1/Arginine Vasopressin; 59865-13-3/Cyclosporine; 7440-70-2/Calcium; 85637-73-6/Atrial Natriuretic Factor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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