Muscarinic signaling pathway in submandibular cells of adult and early postnatal rats.

Elements of the muscarinic signal transduction pathway were compared in submandibular acinar cells of 1-day-old, 1-week-old, and adult rats after exposure to concentrations of acetylcholine ranging from 0.05 to 10 microM. Formation of inositol trisphosphate (IP3) and intracellular Ca2+ were comparable in cells from the three age groups after exposure to agonist concentrations < 1 microM. At higher agonist concentrations, IP3 generation and peak initial changes in [Ca2+]i were significantly greater in cells of newborn animals. In cells of 1-week-old animals, increased peak [Ca2+]i responses were seen even at low agonist concentrations, although IP3 production was not increased when compared with fully mature cells. Increased initial [Ca2+]i peaks, but comparable subsequent plateau [Ca2+]i values, were seen in the immature cells in both Ca(2+)-containing and Ca(2+)-free solutions. Permeabilized cells of early postnatal animals took up less 45Ca2+ into nonmitochondrial Ca2+ pools in the presence of 1.5 mM ATP and also released less tracer in response to intermediate IP3 concentrations than adult cells. Developing salivary cells thus show differences in important functional linkages of the muscarinic signal transduction pathway, including those between receptor activation and phosphoinositide turnover and between IP3 and release of internally stored Ca2+. Differences in the Ca2+ stores or in their sensitivity to IP3 may account for the latter observation. Immature salivary cells seem to have adequate mechanisms for Ca2+ entry.