Involvement of NK1 receptors and importance of the N-terminal sequence of substance P in the stimulation of protein secretion in rat parotid glands

• Published in: European journal of pharmacology Vol. 209; no. 1-2; p. 95
• Main Authors: Rollandy, I, Guillemain, I, Imhoff, V, Drapeau, G, Regoli, D, Rossignol, B
• Format: Journal Article
• Language: English
• Published: Netherlands 10-12-1991
• Subjects: Amino Acid Sequence; Animals; Male; Molecular Sequence Data; Neurokinin A - pharmacology; Neurokinin B - pharmacology; Parotid Gland - drug effects; Parotid Gland - metabolism; Parotid Gland - ultrastructure; Proteins - metabolism; Rats; Rats, Inbred Strains; Receptors, Neurotransmitter - drug effects; Receptors, Neurotransmitter - physiology; Receptors, Tachykinin; Stimulation, Chemical; Substance P - chemistry; Substance P - pharmacology
• ISSN: 0014-2999
• DOI: 10.1016/0014-2999(91)90016-J

Recent in vitro studies have shown that the dose-response curve of substance P on [3H]protein secretion from rat parotid glands is biphasic. Such a response could result either from the activation of tachykinin receptors or from the amphiphilic character of substance P, since it has previously been shown that the N-terminal part of substance P may play an important role in the activation of phosphoinositides in rat parotid glands. To investigate these possibilities, we studied the effects of selective NK1, NK2, NK3 receptor agonists and C-terminal fragments of substance P and neurokinin A on protein secretion from rat parotid lobules. The poor activity of NK2 (neurokinin A-(4-10) and [beta-Ala8]neurokinin A-(4-10)) as well as of NK3 ([MePhe7]neurokinin B) selective agonists allowed us to rule out a possible involvement of NK2 and NK3 receptors in the parotid gland secretory process. Conversely, the selective NK1 receptor agonist, [Sar9,Met(O2)11]substance P, reproduced the biphasic dose-response curve for [3H]protein secretion typical of native substance P. However, a biphasic response was not observed with peptides deprived of the N-terminal moiety of substance P, such as substance P-(4-11) or [AcArg6,Sar9,Met(O2)11] substance P-(6-11). Our data therefore indicate that the [3H]protein secretion obtained with substance P results from the activation of NK1 receptors. Moreover, our data suggest that the N-terminal tripeptide of substance P is also active, and could stimulate different phospholipases either by acting through a second functional site on the NK1 receptor or by directly activating G-proteins.