Characterization of intrathecally administered hemokinin-1-induced nociceptive behaviors in mice.
Hemokinin-1 is a novel mammalian tachykinin cloned from mouse bone marrow. At present, pharmacological profile and physiological role of hemokinin-1 are still unclear. In the present study, we found that intrathecal (i.t.) administration of hemokinin-1 (0.00625-1.6 nmol) induced nociceptive responses consisting of scratching, biting and licking, which resemble substance P-induced behavioral responses in mice. The behaviors evoked by low-dose of hemokinin-1 (0.0125 nmol) were dose-dependently inhibited by i.t. co-administration of CP-99,994, a non-peptidic tachykinin NK(1) receptor antagonist, whereas high-dose of hemokinin-1 (0.1 nmol)-induced behaviors were not affected. Moreover, sendide, a peptidic tachykinin NK(1) receptor antagonist, failed to reduce the behavioral responses of both low- and high-dose of hemokinin-1. In contrast, substance P-induced behaviors were completely suppressed by both CP-99,994 and sendide. These results suggest that hemokinin-1 plays an important role in pain transmission at spinal cord. Moreover, the mechanism of hemokinin-1-induced nociceptive behaviors may be dose-dependent, and distinct from substance P-induced nociceptive behaviors.
Watanabe
Chizuko
C
Department of Physiology and Anatomy, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
Mizoguchi
Hirokazu
H
Yonezawa
Akihiko
A
Sakurada
Shinobu
S
D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D008159:Lumbar Vertebrae / Q000294:innervation*; D008297:Male; D051379:Mice; D064729:Neurokinin-1 Receptor Antagonists; D018377:Neurotransmitter Agents / Q000008:administration & dosage / Q000627:therapeutic use; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D010147:Pain Measurement; D010446:Peptide Fragments / Q000008:administration & dosage / Q000627:therapeutic use; D010880:Piperidines / Q000008:administration & dosage / Q000627:therapeutic use; D011761:Pyrrolidonecarboxylic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D013127:Spinal Nerves / Q000187:drug effects / Q000503:physiopathology*; D013373:Substance P / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000502:physiology / Q000627:therapeutic use; D009435:Synaptic Transmission / Q000187:drug effects*; D015320:Tachykinins / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000502:physiology*; D013997:Time Factors
D000700:Analgesics; D064729:Neurokinin-1 Receptor Antagonists; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D010880:Piperidines; D018040:Receptors, Neurokinin-1; D015320:Tachykinins; C507968:hemokinin-1; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D013373:Substance P; C032292:substance P (6-11); D011761:Pyrrolidonecarboxylic Acid