Muscarinic receptor subtypes in the porcine lung during postnatal development.
The responsiveness of the pulmonary circulation to acetylcholine changes in the newborn piglet. Therefore muscarinic receptors have been studied in the developing porcine lung from birth to adulthood using ligand binding, Northern blotting and in situ hybridisation. Maximal binding capacity of [N-methyl-3H] scopolamine and the affinity of the receptor in lung membranes increased between birth and 16 days (p < 0.05). Subtype affinity changed with age, but always M3, > M1 > M2. Northern blots of porcine muscarinic receptor subtypes showed m1, m2 and m3 mRNA present in lung membranes. m2 mRNA was present at all ages and decreased with age. m1 mRNA was absent at birth and m3 mRNA was absent at 3 days. Autoradiographic localisation showed ligand binding to the parenchyma and airway smooth muscle and nerves, there was no binding to intrapulmonary vessels. In situ hybridisation localised mRNA of all three subtypes to the smooth muscle cells of both vessels and airways. Changes in the receptor subtypes may explain the pharmacological changes during postnatal adaptation.
Hislop
A A
AA
Vascular Biology and Pharmacology Unit, Institute of Child Health, London, UK.
Mak
J C
JC
Reader
J A
JA
Barnes
P J
PJ
Haworth
S G
SG
D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D008168:Lung / Q000254:growth & development / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011869:Radioligand Assay; D011976:Receptors, Muscarinic / Q000235:genetics / Q000378:metabolism*; D013552:Swine
D012333:RNA, Messenger; D011976:Receptors, Muscarinic