A guanine nucleotide-binding protein mediates 1,25-dihydroxy-vitamin D-3-dependent rapid stimulation of Ca2+ uptake in skeletal muscle.
1,25-Dihydroxyvitamin D-3 (1,25(OH)2D3) has been shown to increase Ca2+ uptake readily in skeletal muscle through a dihydropyridine-sensitive pathway, cAMP levels and adenylate cyclase activity. In the present study, fluoride (F-), a potent guanine nucleotide binding protein (G protein) stimulator, rapidly increases vitamin D-deficient skeletal muscle Ca2+ uptake in a dose-dependent manner and with a similar time-course as 1,25(OH)2D3. The increment is detected within 1 min (15%) and steadily increases up to 15 min (60%). The effects of 1,25(OH)2D3 and F- are also observed in muscle from normal, vitamin D-replete chicks. AlCl3, which is required for G protein stimulation by F-, potentiates the effects of F-, Ca2+ uptake in 1,25(OH)2D3-dependent muscle is potentiated by F- and, analogous to the hormone, the effects of F- can be suppressed by Ca(2+)-channel antagonists. Direct exposure of microsomal membranes to 1,25(OH)2D3 reduces the specific binding of [gamma-35S]GTP to the membranes 40%. Pretreatment of muscle with Bordetella pertussis toxin (PTX), known to inhibit Gi, or with cholera toxin (CTX), known to stimulate Gs, produces an acute elevation of muscle Ca2+ uptake. 1,25(OH)2D3 potentiates CTX, but has no additional effect on PTX-dependent Ca2+ uptake. These results indicate that an interaction with an inhibitory G protein coupled to adenylate cyclase may be part of the mechanism by which 1,25(OH)2D3 increase Ca2+ uptake through regulation of Ca(2+)-channel gating by a cAMP-dependent pathway in skeletal muscle.
De Boland
A R
AR
Departamento de Biologia, Universidad Nacional del Sur, Bahia Blanca Argentina.
Flawia
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Coso
O
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Boland
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D037361:Adenylate Cyclase Toxin; D000535:Aluminum / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002117:Calcitriol / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002645:Chickens; D002772:Cholera Toxin / Q000494:pharmacology; D005459:Fluorides / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009132:Muscles / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D037342:Pertussis Toxin; D012508:Sarcolemma / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D015220:Calcium Channels; D010566:Virulence Factors, Bordetella; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D002772:Cholera Toxin; D000535:Aluminum; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D002117:Calcitriol; D009543:Nifedipine; D005459:Fluorides; D002118:Calcium