COMPARISON OF CALCIUM MOBILIZATION IN RESPONSE TO NORADRENALINE AND ACETYLCHOLINE IN SUBMANDIBULAR CELLS OF NEWBORN AND ADULT RATS

The response of mature and immature rat submandibular cells to alpha-r eceptor stimulation was compared in terms of the generation of inosito l triphosphate (IP3) and Ca2+ mobilization, and of how the calcium mob ilization response affects acetycholine (ACh)-induced Ca2+ mobilizatio n. In mature cells, noradrenaline (NA) caused much smaller IP3 and Ca2 + responses than ACh. However, the Ca2+ release induced by NA was enou gh to partially discharge an agonist-sensitive store and to reduce Ca2 + release by a subsequent ACh stimulus. Exposure to NA also caused an influx of Ca2+ in the mature cells, which was largely associated with Ca2+ entry induced by store depletion (i.e. capacitative entry). In th e immature submandibular cells of newborn rats, NA caused essentially no IP3 response and a small Ca2+ release, which only partially affecte d the Ca2+ released by a subsequent exposure to ACh. In contrast to ad ult cells, immature cells did not show an increased Ca2+ influx after exposure to NA. However, prestimulation with this agonist potentiated the Ca2+ flux activated by ACh in the cells of newborn rats, but not i n cells of adult rats. As both mature and immature submandibular cells have a well-developed phosphoinositide turnover response to ACh, the findings in mature cells suggest a less efficient coupling between cc- receptors and phospholipase C, while those in immature cells suggest t hat this coupling is even less functional in the early stages of postn atal development. In permeabilized and Ca-45(2+)-loaded mature cells, cyclic ADP-ribose (cADPR) released 13.4% of loaded Ca-45(2+) and this release was significantly reduced by pre-exposure to IP3. Similarly, p re-exposure to cADPR also reduced the IP3-induced Ca-45(2+) release. I t is concluded that: (1) stimulation with NA induces a smaller Ca2+ re lease in mature and immature submandibular cells than ACh; (2) the med iator for this small Ca2+ mobilization may be cADPR; and (3) NA stimul ates capacitative Ca2+ entry in mature cells, but not in immature cell s, and it also activates a Ca2+ entry pathway distinct from the one in duced by store depletion, particularly in immature cells. (C) 1997 Els evier Science Ltd.