Modulation by Food Restriction of Intracellular Calcium Signaling in Parotid Acinar Cells of Aging Fischer 344 Rats

Abstract

Previous studies suggest that alpha 1-adrenergic (alpha 1-AR)-induced intracellular calcium ([Ca2+]i) mobilization in rat parotid acinar cells declines with age. In this study, we examined the effects of food restriction on alpha 1-AR and muscarinic-stimulated [Ca2+]i mobilization in parotid acinar cells during aging. [Ca2+]i levels in response to the alpha 1-AR agonist epinephrine and the muscarinic agonist carbachol were evaluated in Fura-2-loaded parotid acinar cells from ad libitum-fed (AL) and food-restricted (FR) Fischer 344 male rats at 4, 6, 14, and 24 months of age. [Ca2+]i responses to epinephrine and carbachol (10 microM) were significantly reduced (48% and 35%, respectively; p < .05) in cells from 24-month-old AL rats as compared to younger AL rats. In contrast, no significant reduction of epinephrine and carbachol responses was observed in 24-month-old FR animals. An age-related increase in basal [Ca2+]i (peak around 14 months; p < .02) was observed in both AL and FR rats. In addition, basal [Ca2+]i was higher in FR than in AL rats at 14 and 24 months of age (p < .02). These studies suggest that FR partially attenuates or delays age-related impairments in alpha 1-AR- and muscarinic-cholinergic signal transduction systems of parotid acinar cells. Basal [Ca2+]i also appears to be altered during aging and by FR.

Dysregulation of the B mi‐1/p16 Ink4a pathway provokes an aging‐associated decline of submandibular gland function

“…Thus, it is possible that other factors, such as alterations in receptor function and signal transduction (Olsen et al ., 1997), are involved in the aging-related decline of SMG function. Nonetheless, our findings extend the current understanding of the molecular mechanisms underlying the aging-related decline of SMG function and associated degenerative diseases and will open up new possibilities for its control.…”

“…It is clear that these aging-associated degenerative diseases cannot only be explained by our finding of dysregulation of the Bmi-1/p16 Ink4a pathway because the loss of p16 Ink4a only partially rescued some of the anomalies in Bmi-1-KO SMGs. Thus, it is possible that other factors, such as alterations in receptor function and signal transduction (Olsen et al, 1997), are involved in the aging-related decline of SMG function. Nonetheless, our findings extend the current understanding of the molecular mechanisms underlying the aging-related decline of SMG function and associated degenerative diseases and will open up new possibilities for its control.…”

Cellular Ionic Alterations with Age: Relation to Hypertension and Diabetes

“…Interestingly, this latter observation could equally be a consequence of increased steady‐state basal Cai acting to decrease cellular Ca uptake from the extracellular space 51 . Thus, oxidant stress with H 2 O 2 concomitantly increased Cai levels while decreasing the KCl‐induced rise in Cai by 50%, 40 and aging in Fisher and Wistar rats is also associated with both lesions — basal elevated Cai levels and reduced depolarization‐, epinephrine‐, and carbachol‐stimulated Cai responses 44, 45 …”

Distinct pathways of ERK activation by the muscarinic agonists pilocarpine and carbachol in a human salivary cell line

“…Rat parotid acinar cell aggregates were prepared by a procedure previously utilized in our laboratory (28). Briefly, parotid glands dissected from male Sprague-Dawley rats (250 g body wt; Harlan, Indianapolis, IN) were minced and digested in collagenase-hyaluronidase (100 U/ml and 200 g/ml, respectively) in modified Hanks' balanced salt solution (HBSS) containing 33 mM HEPES and 0.1% FBS with gentle dispersion and gassing (95% O2-5% CO2) every 20 min for 80 min.…”