In the rat parotid gland, an atropine-resistant parasympathetic-nerve-evoked secretion was demonstrated in vivo. In the absence of atropine, the non-adrenergic, non-cholinergic transmitter release seemed to contribute to the fluid secretion and to be largely responsible for the secretion of amylase and acinar secretory granules. The gland was reached by nerve fibers containing substance P (SP), vasoactive intestinal peptide (VIP), and, to some extent, calcitonin-gene-related peptide (CGRP) via the parasympathetic auriculo-temporal nerve. Upon electrical stimulation of the nerve, these peptides were released. SP and substance K (SK), a novel tachykinin, induced a profuse watery secretion when injected i.v., while VIP caused a sparse but amylase-rich secretion. CGRP caused no secretion on its own. The tachykinin-evoked secretory response was enhanced by VIP and CGRP. A SPanalogue almost abolished the SP-evoked response, while the atropine-resistant parasympathetic response was only halved. None of the peptides under study can on its own account for the atropine-resistant parasympathetic secretion. The neuropeptides may play complementary roles in the regulation of the exocrine functions of the gland.
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References
1.
Banns, H.; Ekstrom, J.; and Mann, S.P. (1979): Effects of Duct Ligation on Choline Acetyltransferase Activity in Salivary Glands of Rats, Acta Physiol Scand106:431-435.
2.
Bertaccini, G. and DeCaro, G. (1965): The Effect of Physalaemin and Related Polypeptides on Salivary Secretion. J Physiol Lond181:68-81.
3.
Brodin, E.; Nilsson, G. ; and Folkers, K. (1982): Characterization of Two Substance P Antisera, Acta Physiol Scand114:53-57.
4.
Buck, S.H. and Burcher, E. (1985): The Rat Submaxillary Gland Contains Predominantly P-type Tachykinin Binding Sites, Peptides6:1079-1084.
5.
Butcher, F.R. and Putney, J.W., Jr. (1980): Regulation of Parotid Gland Function by Cyclic Nucleotides and Calcium. In: Advances in Cyclic Nucleotide Research, Vol. 13. P. Greengard and G.A. Robison, Eds., New York: Raven Press, pp. 215-249.
6.
Cascieri, M.A.; Chicchi, C.G.; and Liang, T. (1984): Demonstration of Two Distinct Tachykinin Receptors in Rat Brain Cortex, J Biol Chem260: 1501-1507.
7.
Ekman, R.; Ekstrom, J.; Hakanson, R.; Sjogren, S.; and Sundler, F. (1986): Calcitonin Gene Related Peptide in Rat Salivary Glands, J Physiol Lond381:36P.
8.
Ekstrom, J. (1974): Choline Acetyltransferase Activity in Rat Salivary Glands after Cellulose Rich Diet or Treatment with an Atropine-like Drug, Q J Exp Physiol59:191-199.
9.
Ekstrom, J. and Olgart, L. (1985): Are Both Substance P and Vasoactive Intestinal Peptide Responsible for the Parasympathetically Nerve Evoked Atropine Resistant Salivary Secretion in the Rat? In: Tachykinin Antagonists, R. Håkanson and F. Sundler, Eds., Amsterdam: Elsevier Science Publishers B.V. (Biomedical Division), pp. 241-246.
10.
Ekstrom, J. and Olgart, L. (1986a): Substance P-evoked Salivary Secretion in the Ferret, J Physiol Lond372:41P.
11.
Ekstrom, J. and Olgart, L. (1986b): Complementary Action of Substance P and Vasoactive Intestinal Peptide on the Rat Parotid Secretion. Acta Physiol Scand126:25-31.
12.
Ekstrom, J. and Wahlestedt, C. (1982): Supersensitivity to Substance P and Physalaemin in Rat Salivary Glands after Denervation or Decentralization, Acta Physiol Scand115:437-446.
13.
Ekstrom, J.; Mansson, B.; Tobin, G. ; Garrett, J.R.; and Thulin, A. (1983a): Atropine-resistant Secretion of Parotid Saliva on Stimulation of the Auriculo-temporal Nerve, Acta Physiol Scand119:445-449.
14.
Ekstrom, J.; Mansson, B.; and Tobin, G. (1983b): Vasoactive Intestinal Peptide Evoked Secretion of Fluid and Protein from Rat Salivary Glands and the Development of Supersensitivity , Acta Physiol Scand119:169-175.
15.
Ekstrom, J.; Mansson, B.; and Tobin, G. (1984a): Effects of Atropine or High Frequency Burst Excitation on the Composition of Parasympathetic Rat Parotid Saliva, Acta Physiol Scand122 :409-414.
16.
Ekstrom, J.; Brodin, E.; Ekman, R.; Hakanson, R.; and Sundler, F. (1984b): Vasoactive Intestinal Peptide and Substance P in Salivary Glands of the Rat Following Denervation or Duct Ligation, Reg Peptides10:1-10.
17.
Ekstrom, J.; Brodin, E.; Ekman, R.; Hakanson, R.; Mansson, B.; and Tobin, G. (1985a): Depletion of Neuropeptides in Rat Parotid Glands and Declining Atropine-resistant Salivary Secretion upon Continuous Parasympathetic Nerve Stimulation, Reg Peptides11:353-359.
18.
Ekstrom, J.; Brodin, E.; Ekman, R.; Håkanson, R.; Mansson, B.; and Tobin, G. (1985b): Depletion of Salivary Gland Neuropeptides upon Continuous Parasympathetic Nerve Stimulation,. In: Tachykinin Antagonists, R. Hakanson and F. Sundler, Eds., Amsterdam : Elsevier Science Publishers B.V. (Biomedical Division), pp. 29-33.
19.
Ekstrom, J.; Garrett, J.R.; Månsson, B.; and Tobin, G. (1986): Parotid Degranulation and Amylase Secretion in Rats Caused by Release of Non-Adrenergic Non-Cholinergic Components from the Parasympathetic Nerve, J Physiol Lond372:42 p. Ekstrom, J.; Mansson, B.; and Tobin, G. (1987): Substance K and Salivary Secretion in the Rat , Acta Pharmacol et Toxicol60:1-4.
20.
Emmelin, N. (1967): Nervous Control of Salivary Glands. In: The Handbook of Physiology, Sect. 6, Vol. 11, C.F. Code, Ed., Washington, D.C.: American Physiological Society, pp. 595-632.
21.
Erspamer, V. (1971): Biogenic Amines and Active Polypeptides of the Amphibian Skin. In: Ann Rev Pharmacol, Vol. 11, H.W. Elliot, R. Okun , and R. Dreisbach, Eds., Palo Alto, CA: Annual Reviews, Inc., pp. 327-350.
22.
Fahrenkrug, J. and Schaffalitzky de Muckadell, O.B. (1977): Radioimmunoassay of Vasoactive Intestinal Polypeptide (VIP) in Plasma, J Lab Clin Med89:1379-1387.
23.
Gallacher, D.V. (1983): Substance P is a Functional Transmitter in the Rat Parotid Gland, J Physiol Lond342:483-498.
24.
Grunditz T.; Ekman, R.; Hakanson, R.; Rerup, C.; Sundler, F.; and Uddman, R. (1986): Calcitonin Gene Related Peptide in Thyroid Nerve Fibres and C-Cells. Effects on Thyroid Hormone Secretion and Response to Hypercalcaemia, Endocrinol119:2313-2324.
25.
Hakanson, R. and Sundler, F. (1983): The Design of the Neuroendocrine System: a Unifying Concept and Its Consequences, Trends Pharmacol Sci4:41-44.
26.
Hagele, E.-O.; Schaich, E.; Rauscher, E.; Lehman, P.; Burk, H.; and Wahlefeld, A.-W. (1982): Mechanism of Action of Human Pancreatic and Salivary a-4-Nitrophenyl Maltoheptaoside Substrate, Clin Chem28:2201-2205.
27.
Heidenhain, R. (1872): Ueber die Wirkung einiger Gifte auf die Nerven der Glandula Submaxillaris, Archs Ges Physiol5:309-318.
28.
Hokfelt, T.; Johansson, O.; Kjellert, J.O.; Ljung-Dahl, A.; Nilsson, G.; Nygards, A.; and Pernow, B. (1977): Immunohistochemical Detection of Substance P. In: Substance P, U. S. von Euler and B. Pernow, Eds., New York: Raven Press, pp. 117-145.
29.
Lee, C.M.; Iversen, L.L.; Hanley, M.R.; and Sandberg, B.E.B. (1982): The Possible Existence of Multiple Receptors for Substance P, Naunyn-Schmiedeberg's Arch Pharmacol318 :281-287.
30.
Leeman S.E. and Hammerschlag, R. (1967): Stimulation of Salivary Secretion by a Factor Extracted from Hypothalamic Tissue, Endocrinol81:803-810.
31.
Lembeck, F. and Starke, K. (1968): Substanz P und Speichelsekretion, Naunyn-Schmiedeberg's Arch Pharmak Exp Path258:375-385.
32.
Rudich, L. and Butcher, F.R. (1976): Effect of Substance P and Eledoisin on K+ Efflux, Amylase Release and Cyclic Nucleotide Levels in Slices of Rat Parotid Gland , Biochim Biophys Acta444:704-711.
33.
Scott, J. and Baum, B.J. (1985): Characterization of Secretory Effects of Vasoactive Intestinal Peptide (VIP) in Rat Parotid Cells in vitro, J Dent Res64:681, Abst. 167 (British Division).
34.
Sundler, F.; Brodin, E.; Ekblad, E.; Hakanson, R.; and Uddman, R. (1985): Sensory Nerve Fibres: Distribution of Substance P, Neuorokinin A and Calcitonin Gene-Related Peptide. In: Tachykinin Antagonists, R. Hakanson and F. Sundler, Eds., Amsterdam, Elsevier Science Publishers B.V. (Biomedical Division), pp. 3-14.
35.
Thulin, A. (1976): Motor and Secretory Effects of Nerves on the Parotid Gland of the Rat. Acta Physiol Scand96:506-511.
36.
Uddman, R.; Fahrenkrug, J.; Malm, L.; Alumets, J.; Håkanson, R.; and Sundler, F. (1980): Neuronal VIP in Salivary Glands: Distribution and Release, Acta Physiol Scand110:31-38.
37.
Wharton, J.; Polak, J.M.; Bryant, M.G.; Van Noor-Den, S.; Bloom, S.R.; and Pearse, A.G.E. (1979): Vasoactive Intestinal Polypeptide (VIP)-like Immunoreactivity in Salivary Glands, Life Sci25:273-280.
