Influence of TASP-V, a novel neuropeptide Y (NPY) Y-2 agonist, on nasal and bronchial responses evoked by histamine in anaesthetized pigs and in humans
Dd. Malis et al., Influence of TASP-V, a novel neuropeptide Y (NPY) Y-2 agonist, on nasal and bronchial responses evoked by histamine in anaesthetized pigs and in humans, BR J PHARM, 126(4), 1999, pp. 989-996
1 In nine anaesthetized pigs we have studied the influence of intranasal or
intrabronchial pretreatment with TASP-V, a neuropeptide Y (NPY) Y-2 agonis
t formed by the attachment of NPY 21-36 to a template-assembled synthetic p
eptide (TASP), on the functional responses to subsequent intranasal or intr
abronchial histamine challenge.
2 In a parallel study, subjective and objective nasal airway resistance (NA
R) increase following intranasal histamine challenge was evaluated in II he
althy volunteers after TASP-V or placebo pretreatment.
3 In pigs, increase in sphenopalatine blood flow induced by histamine dihyd
rochloride nasal spray (0.25 mg kg(-1) in 3 mi of saline) was significantly
reduced by 65% (P<0.05) following intranasal pretreatment with 10 mu g kg(
-1) of TASP-V. Bronchoconstriction induced by histamine dihydrochloride neb
ulization (0.5 mg kg(-1) in 3 mi of saline) was significantly attenuated by
25 and 55% following aerosolized pretreatment with TASP-V analogue at 10 a
nd 20 mu g kg(-1), respectively.
4 In healthy volunteers, objective increase in NAR and reduction in nasal m
inimal cross section area (MCSA) induced by intranasal spray of histamine d
ihydrochloride (15 mu g kg(-1) in 200 mu l of saline) were significantly at
tenuated by 50% following local pretreatment with 1.275 mu g kg(-1) of TASP
-V when compared with saline.
5 It is concluded that intranasal or intrabronchial pretreatment with TASP-
V reduced nasal obstruction and bronchoconstriction evoked by histamine cha
llenge in the pig. In healthy human volunteers, this agent attenuated NAR i
ncrease and MCSA reduction induced by intranasal application of histamine.