Noradrenergic innervation does not affect chronic regulation of [ 125I]pindolol receptors in fetal rat brain transplants or host neocortex

Abstract

Fetal (E15–16) somatosensory cortex ( n = 15) or cerebellum ( n = 9) were placed into the somatosensory cortex (SmI) of adult rat hosts to study the relative importance of tissue origin versus host milieu on graft β-adrenoceptor regulation. Autoradiographic studies of [ 125I]pindolol ([ 125I]pin) binding in the presence of 3 μM serotonin were performed as an index of β-receptor binding in both intact hosts and those with ipsilateral locus coeruleus (LC) lesions and/or ipsilateral superior cervical ganglionectomy. [ 125I]pin binding within fetal grafts was highly variable with areas of highest specific binding in cortical grafts (( K d = 209 ± 30pM, B max = 106 ± 7fmol/mg protein) being comparable to host cortex ( K d = 211 ± 41pM, B max = 111 ± 9fmol/mg protein). Average total binding in whole cortical grafts was 73% and in cerebellar grafts was 60% of that in comparable adult cortex. Host cortex had 66–73% and cerebellum had 4–8%β 1-receptors while cortical grafts had 59% and cerebellar grafts had 43%β 1-receptors as determined by competitive binding with ICI 89406 and 118551. Noradrenergic fibers derived from both the host LC and superior cervical ganglion grew into fetal cortical grafts. Binding to high affinity uptake sites ([ 3H]desmethylimipramine, [ 3H]DMI) on noradrenergic terminals in cerebellar grafts was 28% higher than that in cortical grafts; superior cervical ganglionectomy decreased [ 3H]DMI binding in cortical grafts by 37% but had no effect on cerebellar grafts. Neither ganglionectomy nor LC lesions affected total specific binding or binding to β-receptor subtypes in the grafts or host cortex 3–6 months after removal. Therefore, anatomic site of origin appeared to be the predominant factor in determining the development of β-adrenoceptors in fetal cortical tissue. In ectopically placed cerebellar grafts, β-receptor subtypes did not develop comparably to host cerebellar receptors suggesting that host milieu may be of critical importance in receptor development in this tissue.