Calcitonin Receptors in the Central Nervous System of the Rat*

Abstract

Specific binding sites for calcitonin (CT) were sought in preparations of rat brain in vitro. Whole rat brains or discrete regions of the brain were homogenized, and the 10,000 × g fraction was tested for binding of ¹²⁵I-labeled salmon CT ([¹²⁵I]sCT). The highest total and specific binding occurred in the hypothalamus, and the least occurred in the cortex and cerebellum, relative to whole brain. Intermediate levels of binding of the radioligand were found in the pons-midbrain and medulla. More detailed characterization of the hypothalamusradioligand interaction revealed that the binding was saturable and linear with increasing concentrations of tissue protein from 25–800 μg/ml. Furthermore, it was both time and temperature dependent, reaching equilibrium by 1 h at 4, 23, and 37 C. After 1 h of incubation at 4 C, half-maximal inhibition of binding of the radioligand occurred at a sCT concentration of 1 × 10^-9 M. Both porcine and human CT were less effective than sCT in inhibiting the binding of [¹²⁵I]sCT to the hypothalamus. However, ACTH, leucine- and methionine-enkephalin, insulin, GH, parathyroid hormone, and TSH, each at concentrations of 0.5 × 10^-5 M, did not affect the binding of [¹²⁵I]sCT to the hypothalamus. In contrast to its action in peripheral tissues, CT in the brain appeared to inhibit rather than stimulate basal adenylate cyclase activity. These results demonstrate that specific and saturable receptor sites for CT are widely distributed in the central nervous system of the rat, with marked predominance in the hypothalamus, compatible with CT function in these regions. (Endocrinology108: 1672,1981)