Involvement of NK1 receptors and importance of the N-terminal sequence of substance P in the stimulation of protein secretion in rat parotid glands.
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.
Rollandy
I
I
Laboratoire de Biochimie des Transports Cellulaires, CNRS URA 1116, Université Paris-sud, Orsay, France.
Guillemain
I
I
Imhoff
V
V
Drapeau
G
G
Regoli
D
D
Rossignol
B
B
D000595:Amino Acid Sequence; D000818:Animals; D008297:Male; D008969:Molecular Sequence Data; D015288:Neurokinin A / Q000494:pharmacology; D015287:Neurokinin B / Q000494:pharmacology; D010306:Parotid Gland / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D018039:Receptors, Tachykinin; D013268:Stimulation, Chemical; D013373:Substance P / Q000737:chemistry / Q000494:pharmacology*
D011506:Proteins; D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; D013373:Substance P; D015288:Neurokinin A; D015287:Neurokinin B