Maturation of muscarinic agonist receptors in rat developing pancreas and its relation to maximal enzyme secretion

The true K_Ds of [³H] (?) QNB binding to muscarinic receptors were found to be 4.13 and 6.43 × 10^?11 M in pancreas of 21 day fetal and adult rats. The competition curves of specific [³H] (?) QNB bound by two antagonists have shown that the affinity of these drugs did not change with age with Hill coefficients near unity. However, with the agonist carbamylcholine as the competitive drug, a more flat curve was obtained with a Hill coefficient below unity. At least two populations of carbamylcholine binding sites were found with different K_Ds: a K_H around 7 × 10^?7 M and a K_L around 3 × 10^?5 M. These two populations were present during all the developmental periods studied. The ED₅₀ of bethanechol stimulated amylase secretion did not change within the age limit studied (from 11 to 365 days). The high affinity sites for carbamylcholine would seem to be the receptor implicated in the physiological response of the pancreas.