Development of beta-adrenergic receptors and the in vitro accumulation of cyclic AMP in the chick spinal cord.

To clarify the functional development of the descending monoaminergic input to the chick spinal cord we have studied the ontogeny of beta-adrenergic receptors by measuring the specific binding the tritiated dihydroalprenolol (DHA). In addition, we examined the ability of isoproterenol to stimulate the accumulation of cyclic AMP in slices of developing chick spinal cord. Results show that the chick spinal cord contains a high density of beta-adrenergic receptors that are apparently linked to adenylate cyclase. During development, both the density of beta-receptors, as determined by the specific binding of DHA, and the response of tissue slices to isoproterenol underwent marked changes. beta-Adrenergic receptors (approximately 4 fmol/mg tissue) were first detected on the fourteenth day in ovo. Receptor density increased to approximately 20 fmol/mg by day 20. Between day 20 and the time of hatching, a sharp increase in receptor density, to approximately 50 fmol/mg, was seen. The density of receptors remained high until the second day after hatching, fell off to approximately 30 fmol/mg by the fourth day, and remained relatively unchanged through day 30. The response of spinal cord slices to isoproterenol showed a similar pattern of development with the peak response (7-fold increase in levels of cyclic AMP) occurring at or near the time of hatching. During the period between day 18 in ovo and the time of hatching, when both the response of tissue slices to isoproterenol and the density of beta-receptors increased markedly, the activity of phosphodiesterase did not change. Therefore, the pronounced changes in adrenergic responsiveness that occurred near the time of hatching appear to be related primarily to changes in the density of beta-adrenergic receptors coupled to adenylate cyclase. Such developmental changes in the density of beta-adrenergic receptors and adrenergic responsiveness may play an important role in determining the functional state of the descending monoaminergic systems in the chick spinal cord.