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Characterization, Regional Distribution, and Subcellular Distribution of 125 I‐Tyr 1 ‐Somatostatin Binding Sites in Rat Brain
Author(s) -
Epelbaum J.,
Arancibia L. Tapia,
Kordon C.,
Enjalbert A.
Publication year - 1982
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1982.tb06627.x
Subject(s) - somatostatin , binding site , neuropeptide , chemistry , membrane , population , biochemistry , biology , medicine , endocrinology , receptor , demography , sociology
125 I‐Tyr 1 ‐somatostatin binds reversibly, in a saturable manner, and with high affinity to membranes from rat brain. Kinetic and saturation data measured at equilibrium lead to K D values of 0.4 nM for cortical membranes. The binding is not affected significantly by seven neuropeptides and drugs unrelated structurally to somatostatin (SRIF) while native SRIF, Tyr 1 ‐SRIF, and D‐Trp 8 ‐D‐Cys 14 ‐SRIF displace 125 I‐Tyr 1 ‐SRIF in a dose‐dependent manner, with K i of 0.23 n M , 0.90 n M , and 0.11 n M , respectively. Binding sites for 125 I‐Tyr 1 ‐SRIF were found in 9 out of 11 central structures; there was a significant correlation between binding capacity and endogenous SRIF levels measured by radioimmunoassay. In each of the two structures containing the most binding sites, the cortex and the preoptic area, Scatchard analysis suggests a single population of sites with apparent affinities of 0.8 n M and 1.4 n M , respectively. Subcellular fractionation of these two regions reveals that more than 60% of 125 I‐Tyr 1 ‐SRIF specific binding of the homogenate is found in the crude mitochondrial pellet (P 2 ), which contains synaptosomes. When P 2 is further fractionated on a discontinuous sucrose gradient, most of the initial P 2 binding is recovered from membrane fractions. Each of nine SRIF analogs, with a single alanine substitution, displaces 125 I‐Tyr 1 ‐SRIF binding on cortical membranes in the same order of potency as on adenohypophyseal membranes ( r = 0.84). The data demonstrate the presence of SRIF binding sites in the rat brain, with kinetic characteristics comparable to those found in the adenohypophysis, and they provide a biochemical basis for the multiple functions of SRIF in brain.