Ontogenesis and binding properties of high-affinity neurotensin receptors in human brain.
The ontogenesis of neurotensin binding sites was studied in human brain of subjects deceased from Sudden Infant Death Syndrome. Monoiodo-Tyr3 neurotensin specifically recognized 2 distinct classes of binding sites in human brain homogenate. The high affinity sites were already present at birth and increased to a maximal level of 240 fmol/mg protein 1 month after birth. Thereafter, the density of these sites decreased to reach a value of 8 fmol/mg protein in 15-month-old brain, a value similar to that found in adult brain. The dissociation constant of the high-affinity sites (about 0.3 nM) did not vary from birth to adulthood. The high-affinity binding sites were sensitive to GTP which decreased their affinity for neurotensin by a factor of 3, indicating that these sites are functional receptors coupled to GTP-binding proteins. By contrast, the low-affinity sites were insensitive to GTP and could be partly blocked by the antihistaminic drug levocabastine. These sites were absent in human brain during the first post-natal year and could be detected only in brain homogenate of 15-month-old infants. The transient increase in high-affinity neurotensin binding sites after birth suggests that neurotensin could act as a regulatory peptide during brain development.
Zsürger
N
N
Institut de Pharmacologie Moléculaire et Cellulaire du CNRS, Valbonne, France.
Chabry
J
J
Coquerel
A
A
Vincent
J P
JP
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007457:Iodine Radioisotopes; D007700:Kinetics; D051379:Mice; D009496:Neurotensin / Q000378:metabolism*; D011817:Rabbits; D018028:Receptors, Neurotensin; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013398:Sudden Infant Death
D007457:Iodine Radioisotopes; D018028:Receptors, Neurotensin; D017981:Receptors, Neurotransmitter; D009496:Neurotensin; D006160:Guanosine Triphosphate