Development of cholinergic innervation and muscarinic receptor subtypes in piglet trachea.
We studied physiological and pharmacological maturation of cholinergic innervation to tracheal smooth muscle in piglets at three ages: < 7 days, 2-3 wk, and 10 wk. Change in tracheal tension was measured in vivo from a tracheal segment and normalized for its size. Electrical vagal stimulation induced a significantly weaker increase in tracheal tension at < 7 days when compared with 2-3 and 10 wk. In vivo studies employing vagal stimulation before and after topical application of pirenzepine (an M1 muscarinic receptor blocker) and in vitro pharmacological studies evaluating the inhibition of [3H]quinuclidinyl benzilate (QNB) binding by pirenzepine demonstrated that immature M1-receptor function could not account for the weak tracheal smooth muscle responses in the first week. Topical application of the cholinergic agonist methacholine to the tracheal segment also induced a significantly weaker contractile response at < 7 days when compared with 2-3 and 10 wk. Total density of muscarinic receptors, as well as the M1 and M3 muscarinic subtypes, was not statistically different among < 7-day-old, 1- to 3-wk-old, and adult animals. Receptor binding studies in 1-3 wk and adult animals demonstrated biphasic dose-dependent inhibition of [3H]QNB binding in tracheal smooth muscle membranes by methacholine, with a high-affinity component dependent on the availability of G protein. These high-affinity muscarinic receptors coupled to G protein were absent in < 7-day-old piglets. We speculate that the weak tracheal smooth muscle contraction observed during the first week of life is in part secondary to immature G protein function.
Haxhiu-Poskurica
B
B
Department of Pediatrics, Rainbow Babies and Children's Hospital, Cleveland, Ohio.
Ernsberger
P
P
Haxhiu
M A
MA
Miller
M J
MJ
Cattarossi
L
L
Martin
R J
RJ
D000287:Administration, Topical; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D004558:Electric Stimulation; D019204:GTP-Binding Proteins / Q000378:metabolism; D016210:Methacholine Chloride / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D010275:Parasympathetic Nervous System / Q000502:physiology*; D010890:Pirenzepine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000145:classification / Q000378:metabolism*; D013552:Swine; D014132:Trachea / Q000254:growth & development / Q000294:innervation* / Q000378:metabolism*; D014630:Vagus Nerve / Q000502:physiology
D011976:Receptors, Muscarinic; D016210:Methacholine Chloride; D010890:Pirenzepine; D019204:GTP-Binding Proteins