Age differences in cholinergic airway responsiveness in relation with muscarinic receptor subtypes.
Children seem more susceptible to increased airway reactivity than adults. Such an age-dependent discrepancy in airway reactivity may involve different airway smooth muscle functions. Therefore, we compared the in vivo and in vitro responsiveness of airway smooth muscles between two age groups of animals. Rats of 6 and 21 weeks old were challenged in vivo with acetylcholine (ACh) infused intravenously and airway resistance (R(aw)) was measured. Tracheal muscle was also isolated and the isometric force developed to ACh or KCl was measured. Furthermore, the level of genes encoding muscarinic receptor subtypes (M(1-3)) and acetylcholinesterase (AChE) expressed in the tracheal muscle was determined by RT-PCR. In results, the basal R(aw) was similar in the two age groups. The R(aw) at each ACh dose was significantly greater in young rats than older rats (p<0.05, n=22-27). Tracheal muscles from young rats were more sensitive to ACh than older rats (p<0.05, n=20-21), while receptor-independent muscle contraction to KCl was greater in older rats (p<0.05, n=10-19). Genes encoding AChE, M(2) and M(3) muscarinic receptors were more highly expressed in the tracheal muscles from young than older rats (p<0.05, n=4-6). In conclusion, airway smooth muscle in young rat is more sensitive to cholinergic stimulation in vivo and in vitro compared to older rats, which may be due to a higher expression of M(2) and M(3) muscarinic receptors in airway smooth muscle.
Lee
Hye Kyung
HK
Department of Pharmacology, University of Ulsan College of Medicine, Songpagu, Seoul, South Korea. kyung@amc.seoul.kr
Lim
Mi Young
MY
Bok
Se-Mi
SM
Cho
Eui-Sic
ES
Lee
Eun Mi
EM
Kim
Seung Whan
SW
Kim
Young-Hoon
YH
Kim
Hae Won
HW
D000375:Aging / Q000502:physiology*; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000503:physiopathology; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D010275:Parasympathetic Nervous System / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D043585:Receptor, Muscarinic M2 / Q000187:drug effects / Q000378:metabolism; D043587:Receptor, Muscarinic M3 / Q000187:drug effects / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic; D011189:Potassium Chloride