Abstract
In rats anesthetized with urethane, substance P exerts a short-lasting hypotensive effect and stimulates salivary secretion. These effects are significantly increased and prolonged by 5 to 10 times, when substance P is administered in the presence of a mixture of peptidase inhibitors (captopril, thiorphan and phosphoramidon). Ac[Arg 6, Sar 9,Met(O 2) 11]SP(6–11), a selective NK-1 receptor agonist, shows high potency and prolonged hypotensive and sialologic effects. The effects of the NK-1 selective hexapeptide are comparable to those of substance P tested in the presence of peptidase inhibitors and are not modified by peptidase inhibitors. Ac[Arg 6,Sar 9,Met(O 2) 11]SP (6–11) is proposed as a useful tool for studying the roles and functions of NK-1 receptors in vivo, because of its stability, potency and selectivity.
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