Alterations in hepatic adrenergic receptor status in Rana sylvatica in response to freezing and thawing: implications to the freeze-induced glycemic response.

In Rana sylvatica, freeze-induced liberation of glucose from hepatic glycogen stores plays a critical role in conferring freeze tolerance. To determine whether an alteration in hepatic adrenergic receptor status, which dictates catecholamine-directed hepatic glycogenolytic responses, is involved in the glycemic response to freezing, hepatic alpha 1, alpha 2, and beta 2 adrenergic receptors and calcium transport were characterized by radioligand and radioisotopic techniques, respectively, in plasma membranes isolated from the livers of control, -2.5 degrees C-exposed, and frozen-thawed frogs. The three adrenergic receptors display marked and different patterns of changes in response to freezing, with two distinct receptor shifts clearly evident. In the control state, the beta 2 adrenergic receptor dominates over the alpha 1 receptor. At 12 h, beta 2 adrenergic receptor dominance intensifies by a receptor shift involving a decrease in the alpha 1 and alpha 2 adrenergic receptors. Coincident with the initiation of the glycemic response, this early shift may be causally related to it. At 24 h, the alpha 1 adrenergic receptor dominates, achieved by a receptor shift involving a decrease in the beta 2 adrenergic receptor and an increase in the alpha 1 and alpha 2 adrenergic receptors. This shift may be related to the maintenance of the glycemic response. Receptor shifts are associated with changes in calcium transport, which accentuate them. The thawed state is characterized by recovery of alpha, but not beta 2, receptor expression correlatable with, and perhaps allowing, a switch to hepatic glycogenesis. The role of thyroid hormone, whose levels are lower in the frozen state, in inducing receptor shifts is discussed.