Age-related impairment in rat parotid cell alpha 1-adrenergic action at the level of inositol trisphosphate responsiveness.
Alpha 1-Adrenergic-stimulated calcium efflux from rat parotid cell aggregates declines approx. 40% between 3 and 24 months of age, with the bulk of the reduction occurring between 12 and 24 months. Intracellular free calcium levels following alpha 1-adrenoceptor stimulation are also reduced about 40% between 3 and 24 months. No significant age differences in stimulation of inositol mono-, bis- or trisphosphate production are observed. However, the ability of inositol trisphosphate to directly stimulate calcium efflux is reduced by about 50% with increasing age. Concentrations of this inositol phosphate required for maximal calcium release do not change between 3 and 24 months. Differences in response are not due to a reduction in uptake of inositol trisphosphate into older cells, but suggest an age-related defect in the ability of inositol trisphosphate to liberate calcium from intracellular stores. Such dysfunction may be at least partially responsible for impaired alpha 1-adrenergic responsiveness during aging.
Ishikawa
Y
Y
Molecular Physiology and Genetics Section, National Institute on Aging, Francis Scott Key Medical Center, Baltimore, MD 21224.
Gee
M V
MV
Ambudkar
I S
IS
Bodner
L
L
Baum
B J
BJ
Roth
G S
GS
D000367:Age Factors; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D003600:Cytosol / Q000032:analysis; D004837:Epinephrine / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000096:biosynthesis* / Q000494:pharmacology; D008055:Lipids / Q000032:analysis; D008297:Male; D010306:Parotid Gland / Q000187:drug effects / Q000254:growth & development*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D013403:Sugar Phosphates / Q000096:biosynthesis*
D007295:Inositol Phosphates; D008055:Lipids; D011942:Receptors, Adrenergic, alpha; D013403:Sugar Phosphates; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D002118:Calcium; D004837:Epinephrine