Possible existence of a new tachykinin receptor subtype in the guinea pig ileum.
The guinea pig ileum possesses NK-1 and NK-3 tachykinin receptors. As expected, [Pro9]SP and senktide, which are selective agonists of NK-1 and NK-3 receptors, respectively, were found to be highly potent in contracting the guinea pig ileum. Surprisingly, similar observations were made with septide, SP-O-CH3, [Apa9-10]SP, or [Pro9,10]SP although, in contrast to [Pro9]SP, these four peptides showed a low affinity for 3H-[Pro9]SP-specific NK-1 binding sites on membranes from the guinea pig ileum. They were also devoid of affinity for NK-2 and NK-3 binding sites. GR 71251, a compound which has been described as a NK-1 antagonist, was more potent in inhibiting the septide- than the [Pro9]SP-evoked contracting response. Altogether, these results suggest that septide, [Apa9-10]SP, and [Pro9,10]SP exert their high contracting activity in the guinea pig ileum by acting on a new subtype of tachykinin receptors.
Petitet
F
F
Collège de France, INSERM U 114, Chaire de Neuropharmacologie, Paris, France.
Saffroy
M
M
Torrens
Y
Y
Lavielle
S
S
Chassaing
G
G
Loeuillet
D
D
Glowinski
J
J
Beaujouan
J C
JC
D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004600:Eledoisin / Q000031:analogs & derivatives / Q000378:metabolism; D006168:Guinea Pigs; D007082:Ileum / Q000737:chemistry* / Q000187:drug effects; D007202:Indicators and Reagents; D007294:Inositol / Q000378:metabolism; D007457:Iodine Radioisotopes; D009119:Muscle Contraction / Q000187:drug effects; D010306:Parotid Gland / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000032:analysis* / Q000187:drug effects; D018039:Receptors, Tachykinin; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D013388:Succinimides / Q000378:metabolism; D015320:Tachykinins / Q000378:metabolism* / Q000494:pharmacology
C043034:Bolton Hunter-eledoisin ligand; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; D013388:Succinimides; D015320:Tachykinins; D013373:Substance P; D007294:Inositol; D004600:Eledoisin