title: Human eosinophil major basic protein augments bronchoconstriction induced by intravenous agonists in guinea pigs.
abstract: The direct effect of intratracheal (IT) administration of human major basic protein (MBP) on pulmonary inspiratory pressure (PIP), and the effect on agonist-induced change in PIP, were determined in anesthetized, ventilated guinea pigs. 500 micrograms MBP increased PIP from 24.1 +/- 4.3 to 49.8 +/- 7.4 cmH2O (p < 0.002, n = 10). Maximum PIP was achieved within 30 min after 500 micrograms MBP. The direct PIP response to 250 micrograms MBP was not different from vehicle. The PIP responses to intravenous (IV) acetylcholine (Ach) and 5-hydroxytryptamine (5-HT) were measured before and after administration of 250 micrograms MBP (n = 12). MBP caused a modest, but significant potentiation of the increase in PIP induced by 1, 3 and 10 micrograms/kg Ach (24, 32 and 28%, respectively, p < 0.02) and to 1 microgram/kg 5-HT (43% p < 0.02). We conclude that MBP at a dose that does not directly affect inspiratory pressure is capable of augmenting the PIP response to IV Ach and 5-HT in vivo.
authors.affiliation: Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT 06877-0368.
authors.forename: S N
authors.initials: SN
authors.lastname: Desai
authors.forename: G
authors.initials: G
authors.lastname: Van
authors.forename: J
authors.initials: J
authors.lastname: Robson
authors.forename: L G
authors.initials: LG
authors.lastname: Letts
authors.forename: R H
authors.initials: RH
authors.lastname: Gundel
authors.forename: G J
authors.initials: GJ
authors.lastname: Gleich
authors.forename: P J
authors.initials: PJ
authors.lastname: Piper
authors.forename: T C
authors.initials: TC
authors.lastname: Noonan
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000187:drug effects*; D047091:Eosinophil Granule Proteins; D006168:Guinea Pigs; D006801:Humans; D008168:Lung / Q000187:drug effects*; D008297:Male; D012260:Ribonucleases; D012701:Serotonin / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects
chemical_list: D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D012701:Serotonin; D012260:Ribonucleases; D000109:Acetylcholine