Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Substance P binding to cultured anterior pituitary cells was characterized using Bolton-Hunter iodinated substance P as a ligand. At 0 degrees C, the interaction of the ligand and the cellular surface binding sites was found to be specific, rapid and reversible. Scatchard and Hill analysis of specific binding revealed a single class of non-interacting binding sites with a high affinity (KD = 0.48 nM) and a moderate density of binding sites (Bmax = 1187 binding sites/cell). At 37 degrees C a NaOH-soluble intracellular ligand pool was observed in addition to a surface-bound ligand pool released by a low pH buffer. Thus, substance P seems to be internalized after binding to cellular surface binding sites by means of receptor-mediated endocytosis. The internalization was rapid and could be blocked by colchicine (20 microM), an inhibitor of microtubuli assembly. Following internalization, intracellular degradation of the ligand could be demonstrated. Leupeptin (100 microM), an inhibitor of certain lysosomal enzymes could inhibit the cellular degradation of the added ligand, but had only a moderate influence on internalization. These results demonstrate that substance P after binding to a surface-localized receptor on its pituitary target cells is internalized and subsequently degraded by lysosomal enzymes.
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PMID:Binding and internalization of a iodinated substance P analog by cultured anterior pituitary cells. 1247 42

A highly purified preparation of a cation-sensitive neutral endopeptidase was obtained from bovine pituitaries. The enzyme constitutes almost 0.1% of the protein in bovine pituitary homogenates. Polyacrylamide gel electrophoresis of the enzyme showed a single protein band, and in gel filtration experiments on calibrated Sepharose 6B columns the enzyme eluted slightly ahead of thyroglobulin, suggesting an apparent molecular weight of about 700,000. Polyacrylamide gel electrophoresis in SDS-containing buffers indicated the presence of three major components with molecular weights ranging from about 24,000 to 28,000. The enzyme hydrolyzes bonds between hydrophobic and small neutral amino acids in both model synthetic substrates and biologically active peptides such as substance P, LH-RH, and bradykinin. Peptide bonds in which the carbonyl group is contributed by a glutamyl or arginyl residue are also hydrolyzed, especially if they are preceded in the sequence by hydrophobic amino acids. Leupeptin exclusively inhibited enzymatic activity toward the arginine-containing substrates. This observation, together with the high molecular weight and broad specificity of the enzyme, raised the possibility that the isolated enzyme represents a proteolytic complex composed of units with distinctly different activities. Preliminary attempts to dissociate the enzyme into catalytic units of lower molecular weight were not successful and led to loss of activity.
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PMID:Cation-sensitive neutral endopeptidase: isolation and specificity of the bovine pituitary enzyme. 677 72