SP-induced contraction of airway smooth muscle in normal and allergen-sensitized rabbits: mechanism of action.
We studied the mechanisms involved in the airway smooth muscle (ASM) contraction to substance P (SP) in normal (control) and allergen-sensitized (immune) rabbits as well as immune rabbits exposed to allergen via the airways (immune challenged). Cumulative concentration-response curves to SP (1 x 10(-9) to 1 x 10(-4) M) were performed in ASM segments in the absence and presence of atropine (10(-5) M) in vitro. The maximal contractile response (g tension/g tissue) at 10(-4) M SP and ASM contractions at various concentrations of SP were expressed as means +/- SE. We found no difference in the contractile response to SP between control and immune animals. ASM segments obtained from immune-challenged rabbits were more responsive to SP. Atropine shifted to the right the concentration-response curves and decreased the maximal ASM contraction at 10(-4) M SP in all three groups; this effect, however, was greater in immune-challenged tissues. These findings demonstrate an increased contractile response to SP in immune-challenged animals mediated by a more pronounced facilitation of cholinergic neurotransmission. We conclude that the final ASM response to SP is the result of a complex interaction between direct effects on ASM and indirect effects through modulation of cholinergic neurotransmission.
Colasurdo
G N
GN
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, University of Colorado School of Medicine, Denver 80206, USA.
Loader
J E
JE
Graves
J P
JP
Larsen
G L
GL
D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D006967:Hypersensitivity / Q000503:physiopathology*; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D012137:Respiratory System / Q000187:drug effects* / Q000294:innervation / Q000503:physiopathology; D013373:Substance P / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014132:Trachea / Q000187:drug effects
D000485:Allergens; D013373:Substance P; D001285:Atropine