Enkephalinase inhibitors potentiate tackykinin-induced release of /sup 35/SO/sub 4/-labeled macromolecules from ferret trachea
To study the roles of tachykinins and endogenous proteinases in regulating secretion from ferret tracheal glands, the authors measured the release of /sup 35/SO/sub 4/-labeled macromolecules after incubating segments of trachea in Ussing chambers in the presence of /sup 35/SO/sub 4/. 85% of the total macromolecular radioactivity was in fractions of molecular weights greater than or equal to 10/sup 6/. The response to substance P (SP) was concentration-dependent, with a threshold of 10/sup -9/ M, and responses to 10/sup -6/M and 10/sup -5/M of 87 +/- 9 and 156 +/- 26 pmol/cm/sup 2//h, respectively (n = 6 ea). The enkephalinase inhibitor, thiorphan, increased the secretory response to SP (10/sup -6/M) in a concentration-dependent fashion, with a threshold of 10/sup -8/M, and a response to SP after 10/sup -4/M thiorphan of 268 +/- 58 pmol/cm/sup 2//h (p < 0.05; n = 6). Phosphoramidon also increased SP-induced secretion to 334 +/- 69 pmol/cm/sup 2//h (p < 0.005; n = 4), and also potentiated the secretory responses to neurokinins A and B, physalaemin, eledoisin, and kassinin, but did not potentiate the secretory responses to either bradykinin or vasoactive intestinal peptide. Other proteinase inhibitors did not potentiate SP-induced secretion. These results suggest that enkephalinase in the airway degrades tachykinins, and may therefore play a role in regulating tachykinin-induced effects.
- Research Organization:
- Univ. of California, San Francisco
- OSTI ID:
- 5325405
- Report Number(s):
- CONF-8604222-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:3; ISSN FEPRA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
DAYS LIVING RADIOISOTOPES
DOSE-RESPONSE RELATIONSHIPS
ENZYME ACTIVITY
ENZYME INHIBITORS
ENZYMES
EVEN-ODD NUCLEI
HYDROLASES
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAMMALS
METABOLISM
MOLECULAR WEIGHT
NUCLEI
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PEPTIDE HYDROLASES
PEPTIDES
PROTEINS
RADIOISOTOPES
RESPIRATORY SYSTEM
SECRETION
SULFATES
SULFUR 35
SULFUR COMPOUNDS
SULFUR ISOTOPES
TRACER TECHNIQUES
TRACHEA
VERTEBRATES