Somatostatin-28 [1-12]-like peptides.
The search for a peptide corresponding to the NH2-terminus of somatostatin-28 (SS-28) in tissues has led to the isolation and characterization of somatostatin-28[1-12] from pancreas and hypothalamus. Somatostatin-28[1-12]-like immunoreactivity [SS-28 [1-12]-LI] is widely distributed throughout the central nervous system and the digestive system of rodents and primates, reaching levels comparable to those of somatostatin-14 (SS-14). Antibodies directed against the C-terminal end of the dodecapeptide are more specific and constitute excellent markers for the "prosomatostatin" system in mammalian tissues. In rat brain, SS-28[1-12]-LI material is highly concentrated in nerve fibres and terminals, especially in the median eminence, layer I of neocortex, the outer molecular layer of the dentate gyrus and the striatum. Additionally, immunoreactivity is observed in large multipolar or occasionally pyramidal-like neurons of the neocortex. SS-28[1-12] is secreted from hypothalamus and amygdala by a calcium dependent mechanism. No biological role is presently known for the dodecapeptide. Two other peptides of Mr = 8000 (8 K) and Mr = 5000 (5 K) which contain SS-28[1-12] at their carboxy-termini are present in acid extracts from rat pancreas, brain and spinal cord. These two peptides were isolated from an acid extract of rat brains using ion-exchange chromatography, gel permeation chromatography and reverse-phase HPLC. Results from amino acid analysis and partial sequencing were compared to the sequence of the cDNA encoding rat pre-prosomatostatin (prepro-SS) and revealed that the 8 K peptide is a 76 amino acid molecule corresponding to prepro-SS[25-100] and that the 5K peptide, which contains 44 amino acids, corresponds to prepro-SS [57-100]. The 5 K peptide was generated after cleavage of a Leu-Leu bond at position 56-57 of prepro-SS. The four most predominant peptides of the "prosomatostatin system" presently characterized are: SS-14, SS-28[1-12], SS-28 and prepro-SS[25-100]. Studies on pooled perfusates from rat hypothalamic tissue show that prepro-SS[25-100] is released with SS-28[1-12] in vitro and accounts for 22% of the total SS-28[1-12]-like immunoreactive material released during depolarization. The 5 K peptide is apparently not secreted. The presence of prepro-SS[25-100] in brain implies that, first, prosomatostatin can serve as an immediate precursor for SS-14 without going through SS-28 as an intermediate step and second, other peptides could conceivably be derived from the cryptic portion of the precursor.
Benoit
R
R
Bohlen
P
P
Ling
N
N
Esch
F
F
Baird
A
A
Ying
S Y
SY
Wehrenberg
W B
WB
Guillemin
R
R
Morrison
J H
JH
Bakhit
C
C
D000679:Amygdala / Q000378:metabolism; D000818:Animals; D000918:Antibody Specificity; D001921:Brain / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D011498:Protein Precursors / Q000276:immunology / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D013004:Somatostatin / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D053561:Somatostatin-28
D010446:Peptide Fragments; D011498:Protein Precursors; D013004:Somatostatin; D053561:Somatostatin-28; C037197:somatostatin 28-(1-12)