THE ONTOGENY OF [I-125] RAT-ALPHA-CGRP BINDING-SITES IN THE SPINAL-CORD OF SHEEP - A PRENATAL AND POSTNATAL STUDY

In this study we describe the ontogeny of [I-125]rat-alpha-calcitonin gene-related peptide binding sites in the spinal cord of fetal and pos tnatal sheep. The density and distribution of binding sites has been c ompared with the localization of calcitonin gene-related peptide like- immunoreactivity at corresponding stages of development [Nitsos I. and Rees S. (1993) Neuroscience 54, 239-252]. At 68 days of gestation (te rm = 146 days), the earliest fetal tissue examined, there was no evide nce of binding sites in lamina I or the outer regions of lamina II (la mina IIo), although there was a sparse distribution of binding sites i n the inner region of lamina II lamina IIi). By comparison, binding ap peared to be more marked in laminae III-V and more concentrated again in laminae VI-X. This distribution essentially remained constant until 124 days, when there appeared to be a marked increase in the density of binding sites throughout the gray matter, particularly in the dorsa l horn in the lateral extent of both lamina IIo and IIi as well as in laminae III, V and VI. This increase was also observed in the intermed iate zone (lamina VII) and in lamina X. Binding in the ventral horn, w hich was diffuse until this stage, now became particularly dense in th e medial and lateral regions of the horn. From 124 days to one month p ostnatal, there was no marked change in the density or distribution of binding sites. In the adult, binding density decreased slightly throu ghout the spinal cord with the exception of laminae V-VII and lamina X , where the densities were similar to those seen in the neonate. Bindi ng sites were not always coincident with the distribution of immunorea ctivity for calcitonin gene-related peptide. This was particularly evi dent in lamina I and the medial aspect of lamina IIo, where there was an intense expression of calcitonin gene-related peptide but an absenc e of binding sites throughout gestation, in laminae III and IV, where binding sites were present and immunoreactivity absent, and in the ven tral horn up until 104 days, where there was a concentration of bindin g sites in the neuropile but no evidence of immunoreactivity for calci tonin gene-related peptide. In the white matter, prominent binding was associated with the ventral funiculus at 68 days. Binding extended in to the lateral funiculus from 77 to 104 days, after which it was large ly restricted to the dorsolateral fasciculus. Thus, we have shown that binding sites for calcitonin gene-related peptide are present well be fore mid-gestation in the sheep spinal cord and that differences exist between the localization of binding sites and immunoreactivity for ca lcitonin gene-related peptide.