Autonomic receptors in the developing submandibular glands of neonatal rats

Abstract

The functional maturation of the gland during the neonatal period involves specific temporal sequences in the appearance of autonomic membrane receptors and associated changes in the secretory response to receptor stimulation. The density and affinity of cholinergic muscarinic and of α- and β-adrenergic receptors were determined in the glands of 1-, 7-, 14- and 21-day-old rats, using the radioligands [ 3H]-quinuclidinyl benzylate, [ 3H]-prazosin and [ 3H]-dihydroalprenolol for the measurement of muscarinic cholinergic, α 1-adrenergic and β-adrenergic receptors, respectively. The density of binding sites followed similar developmental courses, whether expressed as pmol g tissue or pmol g protein. The densities ( pmol g protein) of β-adrenergic and muscarinic receptors were low in 1-day-old animals, but increased rapidly; adult levels were reached by 2 and 3 weeks of age, respectively. α 1-Adrenergic receptor binding was barely detectable at birth, increased slightly during the first week, dramatically by 14 days and approached adult levels by 21 days. The number of receptors per gland for these 3 autonomic receptor-binding sites increased 50 – 100-fold during the first 3 weeks of postnatal development. The affinities (K D) for each of the three ligands did not differ significantly with age. Surprisingly, the α 2-adrenergic receptor density ( [ 3H]-p- aminoclonidine binding) was high in 1-day-old animals and increased significantly during the first 2 weeks of life. The binding declined after 3 weeks and was nearly undetectable by 6 weeks. Frozen submandibular glands had markedly lower α 2-adrenergic binding compared to fresh glands. These findings suggest that each of the autonomic receptors in rat submandibular glands follows its own specific developmental pattern, and that the appearance of individual receptor types may correlate with the ability of the developing gland to respond to specific stimulants. A K +-release response can be elicited by epinephrine at 2 weeks of age, when α 1 receptor binding sites appear, while both the receptor binding sites and the response to muscarinic agonists are present at birth. As β-adrenergic receptor-binding sites may develop simultaneously with isoproterenol-stimulated adenylate-cyclase activity, it seems that receptor density is important in this response. The functional significance of the high density of α 2-adrenergic receptors in the submandibular gland of neonatal animals is not clear.