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pubmed-article:2825041pubmed:abstractText1. The biological effects of the tachykinins substance P (SP), neurokinin A (NKA) and neuropeptide K (NPK) were studied in relation to their pharmacokinetic properties in the guinea-pig in vivo. 2. NKA and NPK exerted a considerably larger bronchoconstrictor effect than SP. The effect of NPK was slow in onset and had a long duration. The three tachykinins showed similar hypotensive effects although NPK had a longer duration of action than SP and NKA. 3. The disappearance of NPK-like immunoreactivity (-LI) from plasma after i.v. infusion of synthetic NPK was biphasic with apparent half-lives of 0.9 min and 6 min. The plasma half-life of NKA-LI was less than 2 min, while plasma SP-LI was degraded before biochemical analysis could be performed. 4. In guinea-pig plasma at 37 degrees C in vitro, NKA- and NPK-LI were stable for 10 min, while SP-LI disappeared with a half-life of 10 s. 5. Reversed phase HPLC analysis of plasma collected after an i.v. infusion of NPK for 25 min, indicated a partial cleavage of NPK into NKA. 6. It is concluded that potency of the biological effects of SP, NKA and NPK in the guinea-pig in vivo, may not only be attributed to activation of multiple tachykinin receptors but must also be related to the marked differences in pharmacokinetical properties between the tachykinins. Furthermore, whereas SP is rapidly degraded in plasma, NKA and NPK seem to be metabolized in other compartments.lld:pubmed
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pubmed-article:2825041pubmed:articleTitleBronchoconstrictor and hypotensive effects in relation to pharmacokinetics of tachykinins in the guinea-pig--evidence for extraneuronal cleavage of neuropeptide K to neurokinin A.lld:pubmed
pubmed-article:2825041pubmed:affiliationDepartment of Anaesthesia, Karolinska Hospital, Stockholm, Sweden.lld:pubmed
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pubmed-article:2825041pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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