Summary
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1.
Substance P (SP) was infused at different sites of the circulation of the rat. The animal's own salivary response was used as a bioassay to assess the amount of SP not eliminated when SP was infused into different vascular regions.
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2.
The highest degree of elimination of SP occurred in the liver and in the hind limbs, followed by the kidney. Elimination was low in the lungs and absent in the cerebral vessels.
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3.
SP was destroyed by rat plasma in vitro. This was a temperature dependent process.
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4.
Simultaneous infusion of bacitracin potentiated the effect of SP on salivary secretion. The degree of potentiation was dependent on the dose of bacitracin. It acted presumably by inhibiting the enzymatic inactivation of SP in the liver and in peripheral vascular beds. An interaction between bacitracin and SP on the SP receptors of the salivary glands could be excluded.
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5.
In contrast to the pronounced inhibition of the inactivation of SP by bacitracin in vivo, the in vitro inactivation of SP by rat plasma and in the isolated perfused rat hind quarter was hardly influenced by bacitracin. These results indicate an inactivation of circulating SP both by bacitracin sensitive and bacitracin insensitive enzymes.
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6.
The high degree at which SP is eliminated in the liver raises the question whether sufficient intestinal SP with be able to reach a distant organ to exert there a hormonal action or whether the SP present in the intestinal tract acts only locally.
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Preliminary report: Naunyn-Schmiedeberg's Arch. Pharmacol. 302, R 57 (1978)
Supported by grant Nr. 3400 from the Fonds zur Förderung der wissenschaftlichen Arbeit in Österreich
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Lembeck, F., Holzer, P., Schweditsch, M. et al. Elimination of substance P from the circulation of the rat and its inhibition by bacitracin. Naunyn-Schmiedeberg's Arch. Pharmacol. 305, 9–16 (1978). https://doi.org/10.1007/BF00497000
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DOI: https://doi.org/10.1007/BF00497000