The NK-1 receptor and a calcium-phospholipid pathway: inositol trisphosphate production and calcium movements induced by selective agonists of neurokinin receptors in rat parotid glands.
In the rat parotid gland, substance P has been shown to induce a phosphatidylinositol bisphosphate breakdown resulting in an inositol trisphosphate production. These data suggested that substance P activated a phospholipase C and thus mediated its effects through the calcium-phospholipid pathway. To determine which neurokinin (NK) receptor was involved in the substance P response, we have used selective agonists of the different NK receptors and examined their effects on both inositol trisphosphate production and calcium movements. A selective NK-1 receptor agonist, [Sar9Met(O2)11]-substance P, evoked an [3H]inositol trisphosphate production and a rapid and transient 45Ca2+ efflux. On the other hand, selective NK-2 and NK-3 receptor agonists, [beta-Ala8]-NKA(4-10) and [MePhe7]-NKB, respectively, were without effect. We conclude that, in the rat parotid glands, only the NK-1 receptors are coupled to the calcium-phospholipid pathway. The C-terminal part of substance P appeared to be sufficient to stimulate this route because the C-terminal octapeptide, substance P(4-11), mimicked substance P effects on both inositol trisphosphate production and calcium movements. The NK-2 and NK-3 receptors, if present in the rat parotid glands, are not associated with the calcium-phospholipid pathway.
Guillemain
I
I
Laboratoire de Biochimie des Transports Cellulaires, CNRS URA 1116, Université Paris-Sud, Orsay, France.
Rollandy
I
I
Imhoff
V
V
Rossignol
B
B
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000502:physiology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D008297:Male; D010306:Parotid Gland / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D010446:Peptide Fragments / Q000494:pharmacology; D010743:Phospholipids / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology
D010446:Peptide Fragments; D010743:Phospholipids; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; C062618:substance P, Sar(9)-Met(O2)(11)-; D013373:Substance P; C032682:substance P (4-11); D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium