Ascorbate deficiency impairs the muscarinic-cholinergic and beta-adrenergic receptor signaling systems in the guinea pig submandibular salivary gland

Ascorbic acid is preferentially concentrated in the hypothalamus, pituitary and adrenal glands, Its level in the acini of salivary glands is relativel y high. We therefore hypothesized that ascorbate may have a role in salivar y gland function. Ascorbate-deficient guinea pigs had lower stimulated whol e salivary flow rates than well-fed, age-matched controls (P < 0.005). Tota l salivary protein concentration was also markedly (P < 0.005) reduced in t he deficient guinea pigs. SDS-PAGE and densitometric quantification of prot ein bands confirmed significant reduction in specific salivary proteins (e. g., amylase, proline-rich proteins) in the saliva samples of malnourished g uinea pigs. Some protein bands not seen in control saliva were detected in the saliva of malnourished guinea pigs. Ascorbate deficiency also produced a significant (P < 0.005) reduction in the <beta>-adrenergic receptor densi ty (subtype 1; 95 +/- 19 fmol/mg protein compared with 179 +/- 27 fmol/mg p rotein for the controls). No significant difference was observed between th e two groups with respect to the beta -adrenergic receptor subtype 2. Addit ionally, ascorbate-deficient guinea pigs had significantly lower muscarinic -cholinergic receptor densities (50 +/- 5 vs. 74 +/- 8 fmol/mg protein for controls). Our data support the conclusion that diminished membrane recepto rs might impair the capacity of the transmembrane signaling system, resulti ng in salivary gland hypofunction in ascorbate-deficient guinea pigs. Witho ut implying extrapolation of our findings in experimental animals to humans , it is perhaps relevant that many conditions often associated with salivar y gland hypofunction in humans (e.g., smoking or drug ingestion) deplete ce llular ascorbate.