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-receptor stimulation was compared in terms of the generation of inositol triphosphate (IP3) and Ca2+ mobilization, and of how the calcium mobilization response affects acetycholine (ACh)-induced Ca2+ mobilization. In mature cells, noradrenaline (NA) caused much smaller IP3 and Ca2+ responses than ACh. However, the Ca2+ release induced by NA was enough 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 the immature submandibular cells of newborn rats, NA caused essentially no IP3 response and a small Ca2+ release, which only partially affected the Ca2+ released by a subsequent exposure to ACh. In contrast to adult cells, immature cells did not show an increased Ca2+ influx after exposure to NA. However, prestimulation with this agonist potentiated the Ca2+ influx activated by ACh in the cells of newborn rats, but not in 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 alpha-receptors and phospholipase C, while those in immature cells suggest that this coupling is even less functional in the early stages of postnatal development. In permeabilized and 45Ca(2+)-loaded mature cells, cyclic ADP-ribose (cADPR) released 13.4% of loaded 45Ca2+ and this release was significantly reduced by pre-exposure to IP3. Similarly, pre-exposure to cADPR also reduced the IP3-induced 45Ca2+ release. It is concluded that: (1) stimulation with NA induces a smaller Ca2+ release in mature and immature submandibular cells than ACh; (2) the mediator for this small Ca2+ mobilization may be cADPR; and (3) NA stimulates capacitative Ca2+ entry in mature cells, but not in immature cells, and it also activates a Ca2+ entry pathway distinct from the one induced by store depletion, particularly in immature cells.
Wells
J
J
Department of Pediatrics, University of Texas Health Science Center, San Antonio 78284, USA.
Zhang
G H
GH
Martinez
J R
JR
D000109:Acetylcholine / Q000494:pharmacology*; D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects; D036563:Cyclic ADP-Ribose; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism; D013363:Submandibular Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010738:Type C Phospholipases / Q000187:drug effects / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D010716:Phosphatidylinositols; D011942:Receptors, Adrenergic, alpha; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D000109:Acetylcholine; D002118:Calcium; D009638:Norepinephrine