Contribution of tachykinin receptor subtypes to micturition reflex in guinea pigs.
The aim of the present study was to determine the role of tachykinin in the micturition reflex in guinea pigs. We investigated the effects of tachykinin NK(1) receptor antagonists, GR205171 ([2-methoxy-5-(5-trifluoromethyl-tetrazol-1-yl)-benzyl]-(2S-phenyl-piperidin-3S-yl)-amine), CP99994 ((+), (2R, 3R)-3-(2-methoxybenzyl-amino)-2-phenylpiperidine) and FK888 (N(2)-[(4R)-4-hydroxy-1-(1-methyl-1H-indol-3-yl) carbonyl-L-prolyl]-N-methyl-N-phenylmethyl-3-(2-naphthyl)-L-alaninamide), the tachykinin NK(2) receptor antagonist, SR48968 ((+)-N-methyl-[4-(4-acetylamino-4-phenyl piperidino)-2-(3, 4-dichloro-phenyl)butyl] benzamide), and the tachykinin NK(3) receptor antagonist, SB223412 ((S)-(-)-N-(alpha-ethylbenzyl)-3-hydroxy-2-phenylquinoline-4-carboxamide) on rhythmic bladder contraction. GR205171 and CP99994 but not SR48968 or SB223412 reduced bladder contraction frequency. FK888 inhibited the frequency very slightly at the highest dose tested. The distribution of tachykinin NK(1) receptor antagonists to the central nervous system after intravenous administration was examined using an ex vivo binding assay. GR205171 was distributed to the brain and spinal cord, but the tachykinin NK(1) receptor antagonist, FK888, was not. These results suggest that tachykinin NK(1) receptors, which are located in the central nervous system, play an important role in micturition in guinea pigs.
Yamamoto
Takao
T
Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 2-1-6, Kashima, Osaka 532-8514, Yodogawa, Japan. takao_yamamoto@po.fujisawa.co.jp
Hanioka
Naomi
N
Maeda
Yasue
Y
Imazumi
Katsunori
K
Hamada
Kaori
K
Matsuo
Masahiko
M
Manda
Toshitaka
T
Mutoh
Seitaro
S
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D016466:CHO Cells; D002404:Catheterization; D006224:Cricetinae; D004151:Dipeptides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs / Q000502:physiology*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D011869:Radioligand Assay; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D013116:Spinal Cord / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D013373:Substance P / Q000037:antagonists & inhibitors / Q000378:metabolism; D013388:Succinimides / Q000037:antagonists & inhibitors / Q000378:metabolism; D013777:Tetrazoles / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D014020:Tissue Extracts / Q000737:chemistry / Q000494:pharmacology; D014162:Transfection / Q000379:methods; D001743:Urinary Bladder / Q000502:physiology; D014554:Urination / Q000187:drug effects / Q000502:physiology*
C043194:Bolton Hunter reagent-substance P conjugate; D004151:Dipeptides; D007211:Indoles; D007457:Iodine Radioisotopes; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018040:Receptors, Neurokinin-1; D013388:Succinimides; D013777:Tetrazoles; D014020:Tissue Extracts; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; C078949:FK 888; D013373:Substance P; C103207:vofopitant