RESUMO
In the present study, highly specific radioimmunoassays were developed and used to measure neurokinin B, neurokinin A and substance P in the rat spinal cord and various peripheral tissues. The results are as follows. (1) Neurokinin B and neurokinin A were distributed all along the rostrocaudal axis of the spinal cord, as is substance P, and were more concentrated in the dorsal than in the ventral region. (2) Substance P was more abundant in the central and peripheral nervous tissues than neurokinin A, while in certain peripheral organs, neurokinin A was more abundant than substance P. In the spinal cord, neurokinin B concentrations were lower than those of the other two tachykinins. (3) In contrast to neurokinin A and substance P, neurokinin B was not detected in any of the peripheral tissues examined. (4) Capsaicin treatment reduced by half neurokinin A and substance P concentrations in the dorsal region of the spinal cord, the dorsal root ganglia and the sciatic nerve, but was without effect on neurokinin B concentrations in the spinal cord. Neurokinin A, like substance P, may therefore have an important function in the transmission of sensory information, particularly in nociceptive transmission from the periphery to the spinal cord and in peripheral neurogenic inflammation. In contrast, since neurokinin B was not found in the sensory neurons, it is not likely to have these functions, but may perhaps control them.
Assuntos
Capsaicina/farmacologia , Gânglios Espinais/metabolismo , Neurocinina A/metabolismo , Neurocinina B/metabolismo , Nervo Isquiático/metabolismo , Medula Espinal/metabolismo , Substância P/metabolismo , Animais , Animais Recém-Nascidos , Gânglios Espinais/efeitos dos fármacos , Cobaias , Masculino , Neurocinina A/análise , Neurocinina B/análise , Especificidade de Órgãos , Radioimunoensaio , Ratos , Ratos Endogâmicos , Nervo Isquiático/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Substância P/análiseRESUMO
RP 67580, a non-peptide NK1 receptor antagonist, inhibited in a stereoselective and dose-dependent manner plasma extravasation caused in the dura mater by intravenous injection of capsaicin in guinea-pigs and of exogenous substance P in rats (ED50 = 35 and 2.5 micrograms/kg i.v., respectively). In the two species, RP 67580 appeared to be more effective in the dura mater than in the peripheral organs. These results indicate that selective NK1 receptor antagonists could be potentially effective for the treatment of migraine headache.