Differential effects of substance P analogs on neurokinin 1 receptor agonists in the mouse spinal cord.
Effects of five substance P (SP) analogs on the licking, biting and scratching response induced by neurokinin (NK) 1 receptor agonists such as SP, physalaemin and (p-Glu6,Pro9)-SP (6-11) (septide) were studied after intrathecal injections in mice. Septide brought about a SP-like behavioral response, and was approximately 25 times more potent than the D-Pro9 analog, D-septide. When administered simultaneously with NK-1 receptor agonists, a putative SP antagonist, spantide inhibited SP-, physalaemin- and septide-induced behavioral response in a dose-dependent manner with ED50 values of 1.0, 0.65 and 1.3 nmol/mouse, respectively. Septide-induced response was significantly reduced by lower doses of (D-Arg1, D-Pro2,4, D-Phe7, D-His9, Leu11)-SP than (D-Phe7, D-His9, Leu11)-SP (6-11). In contrast, (D-Arg1, D-Pro2,4, D-Phe7, D-His9)-SP (0.5-1.0 nmol) and (D-Phe7, D-His9)-SP (6-11) (0.5-2.0 nmol) inhibited only SP-induced behavioral response, but not physalaemin- or septide-induced response. The results of this study indicate that NK-1 receptor agonists are not necessarily affected to a same degree by SP analogs containing D-His. These findings may be interpreted as indicative of the existence of different NK-1 receptor subtypes.
Sakurada
T
T
Department of Pharmacology, Tohoku College of Pharmacy, Sendai, Japan.
Yamada
T
T
Tan-no
K
K
Manome
Y
Y
Sakurada
S
S
Kisara
K
K
Ohba
M
M
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000037:antagonists & inhibitors*; D010803:Physalaemin / Q000037:antagonists & inhibitors*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D013116:Spinal Cord / Q000187:drug effects*; D013373:Substance P / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000700:Analgesics; D010446:Peptide Fragments; D010803:Physalaemin; D013373:Substance P; C054725:septide; C042867:spantide; D011761:Pyrrolidonecarboxylic Acid