Potentiation of the contractile effects of neuropeptides in human bronchus by an enkephalinase inhibitor.
Many neuropeptides have been identified in human airways and these are susceptible to breakdown by endogenous enkephalinases. This study investigated the effect of enkephalinase inhibition with phosphoramidon (10(-5) M) on contractile responses to neurokinin A, eledoisin, physalaemin and substance P in human isolated bronchial smooth muscle. Contractile responses to the maximal doses of neuropeptides given were potentiated by phosphoramidon, whereas those to carbachol were unaffected. In addition, neuropeptide response curves were significantly (P less than 0.05) shifted to the left as measured by geometric mean dose ratios (95% confidence intervals) of 20.9 (5.4-81.3) n = 7 for neurokinin A; 63 (21.8-181.9) n = 6 for eledoisin, 44.7 (3.2-616.6) n = 5 for physalaemin and 6.9 (2.4-20) n = 6 for substance P. We conclude that enkephalinase inhibition in vitro significantly potentiates the contractile response to neuropeptides in human airway smooth muscle. Absence of, or decreased activity of enkephalinase could lead to enhanced effects of endogenous neuropeptides in human airways in vivo.
Black
J L
JL
Department of Pharmacology, University of Sydney, NSW Australia.
Johnson
P R
PR
Armour
C L
CL
D001980:Bronchi / Q000187:drug effects*; D016085:Bronchoconstrictor Agents / Q000494:pharmacology*; D004357:Drug Synergism; D006020:Glycopeptides / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D009479:Neuropeptides / Q000494:pharmacology*
D016085:Bronchoconstrictor Agents; D006020:Glycopeptides; D009479:Neuropeptides; D015260:Neprilysin; C008890:phosphoramidon