Modulation of rat parotid cell alpha-adrenergic responsiveness at a step subsequent to receptor activation.
Parotid gland acinar cells, prepared from 12- and 24-month-old rats, show decreased physiological responsiveness to alpha-adrenergic stimulation in vitro compared to cells from 3-month-old rats. K+ efflux, an index of water and electrolyte secretion, was approximately 35% lower with 12- and 24-month-old parotid cells. No loss of alpha-adrenergic receptors, their binding affinity for specific alpha-adrenergic ligands, or their relative subtype distribution, accompanied the diminished exocrine function. Conversely, a significant reduction in alpha-adrenergic-mediated phospholipid turnover in, and 45Ca2+ efflux from, parotid cells of older rats was observed. These changes in phospholipid metabolism and Ca2+ flux were parallel to changes seen in K+ efflux as judged by dose-response studies. When the alpha-adrenergic receptor was by-passed by using the Ca2+-ionophore A-23187 to elicit K+ efflux, young and old parotid cells were equally responsive. In aggregate the findings suggest that parotid gland cells from older rats display an altered alpha-adrenergic signal transduction mechanism at a site between the receptor and phospholipid turnover/Ca2+ mobilization.
D000375:Aging; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology*; D008297:Male; D010306:Parotid Gland / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D010761:Phosphorus Radioisotopes / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*
D010712:Phosphatidic Acids; D010716:Phosphatidylinositols; D010761:Phosphorus Radioisotopes; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D000001:Calcimycin; D011188:Potassium; D002118:Calcium; D004837:Epinephrine