N-terminal substance P fragments inhibit the spinally induced, NK 1 receptor mediated behavioural responses in mice.
N-terminal fragments of substance P (SP) were tested for antagonism against the aversive responses induced in mice by various tachykinin receptor agonists, somatostatin and bombesin. When co-administered with SP intrathecally, low doses (1.0-4.0 pmol) of SP (1-7) or SP (1-8) reduced the SP-induced behavioural responses of scratching, biting and licking. Aversive responses induced by two other neurokinin (NK) 1 receptor agonists, Septide and physalaemin, were also dose-dependently decreased by the simultaneous injection of small doses of SP (1-7) or SP (1-8). Aversive responses induced by 400 pmol of NK A were also significantly reduced by co-administration of SP (1-7) or SP (1-8). No significant effects of the N-terminal fragments were observed against the aversive responses elicited by NK A (300 pmol), eledoisin, NK B, somatostatin or bombesin. These results suggest that the behavioural antagonism produced by SP (1-7) and SP (1-8) may be limited to the NK 1 receptor at the spinal level in mice.
Sakurada
T
T
Department of Pharmacology, Tohoku College of Pharmacy, Sendai, Japan.
Tan-No
K
K
Yamada
T
T
Sakurada
S
S
Kisara
K
K
Ohba
M
M
Terenius
L
L
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001839:Bombesin / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000502:physiology*; D013004:Somatostatin / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D013373:Substance P / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D015320:Tachykinins / Q000037:antagonists & inhibitors / Q000494:pharmacology
D010446:Peptide Fragments; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D015320:Tachykinins; D013373:Substance P; D013004:Somatostatin; C054725:septide; D001839:Bombesin; D011761:Pyrrolidonecarboxylic Acid