It is very well established that the principal control of salivary secretion is derived from autonomic innervation. Transmission of a neural signal to a salivary gland acinar cell occurs chemically via neurotransmitters, the first messengers of a secretory response. Neurotransmitters bind to specific cell surface receptor proteins, an event which activates precise transduction mechanisms which then transfer the neural signal to the inside of the cell. There are two major transduction mechanisms operative in salivary gland acinar cells. One involves the generation of cAMP, the other involves the breakdown of plasma membrane polyphosphoinositides. For both mechanisms, the appropriate stimulated receptor activates a second plasma membrane protein, termed an N (or G) protein. The N protein requires GTP to activate an enzyme (adenylate cyclase or phospholipase C), which then catalyzes the formation of a second messenger (cAMP and inositol trisphosphate/diacylglycerol, respectively). This action provides the intracellular signal for secretory events (protein, fluid, electrolyte secretion) to begin.
Get full access to this article
View all access options for this article.
References
1.
AbeK., and DAWESC. (1982): Secretion of Protein by the Submandibular Glands of the Rat, Mouse, and Hamster in Response to Various Parasympatho- and Sympathomimetic Drugs, J Dent Res61: 1454–1457.
2.
AuD.K.; MALBONC.C.; and BUTCHERF.R. (1977): Identification and Characterization of Beta1-Adrenergic Receptors in Rat Parotid Membranes, Biochim Biophys Acta500: 361–371.
3.
AubD.L. and PUTNEYJ.W.Jr. (1985): Properties of Receptor-controlled Inositol Trisphosphate Formation in Parotid Acinar Cells, Biochem J225: 263–266.
4.
BAUMB.J.; COLPOF.T.; and FILBURNC.R. (1981a): Characterization and Relationship to Exocrine Secretion of Rat Parotid Gland Cyclic AMP-Dependent Protein Kinase, Arch Oral Biol26: 333–337.
5.
BAUMB.J.; FREIBERGJ.M.; ItoH.; ROTHG.S.; and FILBURNC.R. (1981b): β-Adrenergic Regulation of Protein Phosphorylation and its Relationship to Exocrine Secretion in Dispersed Rat Parotid Gland Acinar Cells, J Biol Chem256: 9731–9736.
6.
BAUMB.J. (1986): Regulation of Salivary Secretion: In: The Salivary System, SreebnyL., Ed., Boca Raton, FL: CRC Press(in press).
7.
BERRIDGEM.J. (1984): Inositol Trisphosphate and Diacylglycerol as Second Messengers, Biochem J220: 345–360.
8.
BERRIDGEM.J. (1985): The Molecular Basis of Communication within the Cell. Sci American253(4): 142–152.
9.
BLACKMOREP.F.; BOCCKINOS.B.; WAYNICKL.E.; and EXTONJ.H. (1985): Role of a Guanine Nucleotide-binding Regulatory Protein in the Hydrolysis of Hepatocyte Phosphatidylinositol 4.5-Bisphosphate by Calcium-mobilizing Hormones and the Control of Cell Calcium. J Biol Chem260: 14477–14483.
10.
BROWNJ.H.; GOLDSTEIND.; and MASTERSS.B. (1985): The Putative M1 Muscarinic Receptor Does Not Regulate Phosphoinositide Hydrolysis, Molec Pharmacol27: 525–531.
11.
BUTCHERF.R. (1980): Regulation of Calcium Efflux from Isolated Rat Parotid Cells, Biochim Biophys Acta630: 254–260.
12.
BUTCHERF.F.; GOLDMANJ.A.; and NEMEROVSKIM. (1975): Effect of Adrenergic Agents on α-Amylase Release and Adenosine 3’, 5‘-monophosphate Accumulation in Rat Parotid Slices, Biochim Biophys Acta392: 82–94.
13.
DEHAYEJ.P.; CHRISTOPHEJ.; ERNSTF.; POLOCZEZKP.; and VAN BOGAERTP. (1985): Binding in vitro of Vasoactive Intestinal Peptide on Isolated Acini of Rat Parotid Gland, Arch Oral Biol30: 827–832.
14.
EMMEL1NN. (1972): Control of Salivary Glands. In: Oral Physiology, EmmelinN., and ZottermanY., Eds., Oxford: Pergamon Press, pp. 1–16.
15.
EvaC.; MEEKJ.L.; and COSTAE. (1985): Vasoactive Intestinal Peptide which Coexists with Acetylcholine Decreases Acetylcholine Turnover in Mouse Salivary Glands. J Pharmacol Exp Ther323: 670–674.
16.
FRASERC.M. and VENTERJ.C. (1982): The Size of the Mammalian β2-Adrenergic Receptor as determined by Target Size Analysis and Immunoaffiinity Chromatography, Biochem Biophys Res Commun109: 21–29.
17.
GARRETTJ.R. (1982): Adventures with Autonomic Nerves. Perspectives in Salivary Glandular Innervations, Proc R Micr Soc17: 242–253.
18.
GILMANA.G. (1984): Guanine Nucleotide-binding Regulatory Proteins and Dual Control of Adenylate Cyclase, J Clin Invest73: 1–4.
19.
HAVELR.J. (1986): Functional Activities of Hepatic Lipoprotein Receptors, Ann Rev Phvsiol48: 119–134.
20.
HELMANJ.; KUYATTB.L.; TAKUMAT.; SELIGMANNB.; and BAUMB.J. (1986): ATP-Dependent Calcium Transport in Rat Parotid Basolateral Membrane Vesicles: Modulation by Agents Which Elevate Cyclic AMP, J Biol Chem261: 8919–8923.
21.
HERRONG.S., and SCH1MERLIKM.I. (1983): Glycoprotein Properties of the Solubilized Atrial Muscarinic-Cholinergic Receptor, J Neurochem41: 1414–1420.
22.
HOKINM.R. and HOKINL.E. (1953): Enzyme Secretion and the Incorporation of 32P into Phospholipids of the Pancreas, J Biol Chem203: 967–977.
23.
HOLLENBERGM.D. (1979): Hormone Receptor Interactions at the Cell Membrane, Pharmueol Rev30: 393–410.
24.
INOUEY. and KANNOT. (1982): Secretory Effects of VIP. Adrenaline and Carbachol in Isolated Lobules of the Rat Parotid Gland, Biomed Res3: 384–389.
25.
ItoH.; BAUMB.J.; and ROTHO.S. (1981): β-Adrenergic Regulation of Rat Parotid Gland Exocrine Protein Secretion During Aging. Mech Ageing Develop15: 177–188.
26.
ItoH., HOOPESM.T.; BAUMB.J.; and ROTHG.S. (1982): K+-Release from Rat Parotid Cells: an α1-Adrenergic Mediated Event. Biochem Pharmacol31: 567–573.
27.
JAHNR. and SÖLINGH.-D. (1981): Phosphorylation of the Same Specific Protein During Amylase Release Evoked by β-Adrenergic or Cholinergic Agonists in Rat and Mouse Parotid Glands, Proc Natl Acad Sci USA78: 6903–6906.
28.
JAHNR.; UNGERC.; and SOLINGH.-D. (1980): Specific Protein Phosphorylation During Stimulation of Amylase Secretion by β-Agonists or Dibutyryl Adenosine 3’,5’-monophosphate in the Rat Parotid Gland. Eur J Biochem112: 345–352.
29.
JOSEPHS.K. (1985): Receptor-stimulated Phosphoinositide Metabolism: a Role for GTP-Binding Proteins. Trends Biochem Sci10: 297–298.
30.
KAHNC.R. (1985): The Molecular Mechanism of Insulin Action, Ann Rev Med36: 429–451.
31.
KLOOGY.; HOROWITZM.; MEIRIU.; GALRONR.; and AVRONA. (1985): Regulation of Submaxillary Gland Muscarinic Receptors during Heat Acclimation, Biochim Biophys Acta845: 428–435.
LIANGT., and CASCIERIM.A. (1980): Specific Binding of an Immunoreactive and Biologically Active l25I-labeled N(l) Acetylated Substance P Derivative to Parotid Cells. Biochem Biophvs Res Commun96: 1793–1799.
34.
LONDOSC.; SALOMONY.; LinM.; HARWOODJ.P.; SCHRAMMM.; WOLFFJ.; and RODBELLM. (1974): 5‘-Guanylylimido-diphos-phate, a Potent Activator of Adenylate Cyclase Systems in Eukaryotic Cells, Proc Natl Acad Sci USA71: 3087–3090.
35.
LOUIED.S. and OWYANGC. (1986): Muscarinic Receptor Subtypes on Rat Pancreatic Acini: Secretion and Binding Studies. Am J Physiol251: G275–G279.
36.
LUDFORDJ.M. and TALAMOB.R. (1980): β-Adrenergic and Muscarinic Receptors in Developing Rat Parotid Glands, J Biol Chem255: 4619–4627
ORLYJ., and SCHRAMMM. (1976): Coupling of Catecholamine Receptor from One Cell with Adenylate Cyclase from Another Cell by Cell Fusion, Proc Nail Acad Sci USA73: 4410–4414.
39.
POINTONS.E. and BANERJEES.P. (1979): Alpha- and Beta-Adrenergic Receptors of the Rat Salivary Gland, Biochim Biophvs Ada584: 231–241.
40.
PUTNEYJ.W.Jr., and VAN DE WALLEC.M. (1980): The Relationship Between Muscarinic Receptor Binding and Ion Movements in Rat Parotid Cells, J Phvsiol Lond299: 521–531.
41.
PUTNEYJ.W.Jr.; McKINNEYJ.S.; AubD.L.; and LESLIEB.A. (1984): Phorbol Ester-induced Protein Secretion in Rat Parotid Gland. Molec Pharmacol26: 261–266.
42.
PUTNEYJ.W.Jr. (1986): Identification of Cellular Activation Mechanisms Associated with Salivary Secretion, Ann Rev Physiol48: 75–88.
43.
ROBINSONS.E.; SCHWARTZJ.P.; and COSTAE. (1980): Substance P is in the Superior Cervical Ganglion and the Submaxillary Gland of the Rat, Brain Res182: 11–17.
44.
ROSCHERA.A.; WIESMANNU.N.; and HONEGGERU.C. (1981): Changes in Beta Adrenergic Receptors in Submaxillary Glands of Chronically Reserpine- or Isoproterenol-treated Rats, J Pharmacol Exp Ther216: 419–424.
45.
SCHNEYERL.H., and EMMEL1NN. (1974): Salivary Secretion. In: Gastrointestinal Physiology, JacobsonE.D., and ShambourL.L., eds., London: Butterworths, pp. 183–226.
SCOTTJ., and BAUMB.J. (1985): Involvement of Cyclic AMP and Calcium in Exocrine Protein Secretion Induced by Vasoactive Intestinal Polypeptide in Rat Parotid Cells, Biochim Biophvs Ada847: 255–262.
48.
SMITHC.D.; CoxC.C.; and SNYDERMANR. (1986): Receptor-coupled Activation of Phosphoinositide-specific Phospholipase C by an N Protein, Science232: 97–100.
49.
STILESG.L.; BENOVICJ.L.; CARONM.G.; and LEFKOWITZR.J. (1984): Mammalian β-Adrenergic Receptors. Distinct Glycoprotein Populations Containing High Mannose or Complex Type Carbohydrate Chains. J Biol Chem259: 8655–8663.
50.
STREBH.; IRVINER.F.; BERRIDGEM.J.; and SCHULTZI. (1983): Release of Ca2 ’ from a Nonmitochondrial Intracellular Store in Pancreatic Acinar Cells by Inositol-1,4,5-Trisphosphate, Nature306: 67–69.
51.
STRITTMATTERW.J.; DAVISJ.N.; and LEFKOWITZR.J. (1977): α-Adrenergic Receptors in Rat Parotid Cells. J Biol Chem252: 5472–5477.
52.
THAYSENJ.H.; THORNN.A.; and SCHWARTZI.L. (1954): Excretion of Sodium, Potassium, Chloride and Carbon Dioxide in Human Parotid Saliva. Am J Physiol178: 155–159.
53.
VAN DER VENP.F.; TAKUMAT.; and BAUMB.J. (1986): Chlorpromazine Inhibition of Muscarinic-cholinergic Responses in Rat Parotid Gland. J Dem Res65: 382–386.
54.
VAN DOPC. and BOURNEH.R. (1983): Pseudohypoparathyroidism, Ann Rev Med34: 259–266.
YOUNGJ.A., and VAN LENNEPE.W. (1979): Transport in Salivary and Salt Glands. In: Membrane Transport in Biology, GiebischG., TostesonD.C., and UssingH.H., Eds., Berlin: Springer-Verlag, pp. 563–674.
