Document Detail


Cellular signaling by cyclosporine A in contractile cells: interactions with atrial natriuretic peptide.
MedLine Citation:
PMID:  8461628     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
H Meyer-Lehnert; D Bokemeyer; U Friedrichs; S Drechsler; H J Kramer
Related Documents :
18469148 - Intradermal angiotensin ii administration attenuates the local cutaneous vasodilator he...
3818628 - Spatially resolved cytosolic calcium response to angiotensin ii and potassium in rat gl...
3966548 - Effects of ang ii and k+ on ca efflux and aldosterone production in adrenal glomerulosa...
7507838 - Functional specificity for salmon gonadotropin-releasing hormone (gnrh) and chicken gnr...
16594678 - Microcontainers with electrochemically reversible permeability.
8824228 - A heparin-sensitive phospholipase a2 and prostaglandin endoperoxide synthase-2 are func...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Clinical investigator     Volume:  71     ISSN:  0941-0198     ISO Abbreviation:  Clin Investig     Publication Date:  1993 Feb 
Date Detail:
Created Date:  1993-05-04     Completed Date:  1993-05-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9207154     Medline TA:  Clin Investig     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  153-60     Citation Subset:  IM    
Affiliation:
Medizinische Poliklinik, Universität Bonn.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Angiotensin II / 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:
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


Previous Document:  Aneurysms of coronary arteries in a patient with adult polycystic kidney disease: arteriosclerosis o...
Next Document:  Allopurinol and oxypurinol in human breast milk.