Influence of TASP-V, a novel neuropeptide Y (NPY) Y2 agonist, on nasal and bronchial responses evoked by histamine in anaesthetized pigs and in humans.
1. In nine anaesthetized pigs we have studied the influence of intranasal or intrabronchial pretreatment with TASP-V, a neuropeptide Y (NPY) Y2 agonist formed by the attachment of NPY 21-36 to a template-assembled synthetic peptide (TASP), on the functional responses to subsequent intranasal or intrabronchial histamine challenge. 2. In a parallel study, subjective and objective nasal airway resistance (NAR) increase following intranasal histamine challenge was evaluated in 11 healthy volunteers after TASP-V or placebo pretreatment. 3. In pigs, increase in sphenopalatine blood flow induced by histamine dihydrochloride nasal spray (0.25 mg kg(-1) in 3 ml of saline) was significantly reduced by 65% (P<0.05) following intranasal pretreatment with 10 microg kg(-1) of TASP-V. Bronchoconstriction induced by histamine dihydrochloride nebulization (0.5 mg kg(-1) in 3 ml of saline) was significantly attenuated by 25 and 55% following aerosolized pretreatment with TASP-V analogue at 10 and 20 microg kg(-1), respectively. 4. In healthy volunteers, objective increase in NAR and reduction in nasal minimal cross section area (MCSA) induced by intranasal spray of histamine dihydrochloride (15 microg kg(-1) in 200 microl of saline) were significantly attenuated by 50% following local pretreatment with 1.275 microg 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 challenge in the pig. In healthy human volunteers, this agent attenuated NAR increase and MCSA reduction induced by intranasal application of histamine.
Malis
D D
DD
Laboratory of Experimental Rhinology, Clinic of Otorhinolaryngology, University Hospital, Geneva, Switzerland.
Grouzmann
E
E
Morel
D R
DR
Mutter
M
M
Lacroix
J S
JS
D000328:Adult; D000758:Anesthesia; D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D016084:Bronchoconstriction / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000187:drug effects* / Q000502:physiology; D009478:Neuropeptide Y / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D017476:Receptors, Neuropeptide Y / Q000819:agonists*; D013373:Substance P / Q000502:physiology; D013552:Swine
D009478:Neuropeptide Y; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D013373:Substance P; D006632:Histamine; D015740:Calcitonin Gene-Related Peptide