Rapid sequestration and degradation of somatostatin analogues by isolated brain microvessels.

摘要: Somatostatin (SRIF) is a putative peptide neurotransmitter that may interact with brain capillaries following neurosecretion of the peptide. The present studies investigate binding and metabolism SRIF analogues in isolated bovine microvessels. 125I-[Tyr1]SRIF was rapidly degraded by capillary aminopeptidase half-time approximately 3 min at 23 degrees C. microvessel had low affinity high capacity for peptide, Km = 76 microM Vmax 74 nmol min-1 mgp-1. 125I-[Tyr11]SRIF converted to free iodotyrosine much slower rate, presumably lower-activity endopeptidase. 125I-[Try11]SRIF bound microvessels, whereas another basic [Tyr8]bradykinin, or an acidic CCK8, neutral leucine enkephalin, were considerably less extent. nonsaturable up concentration 1 microgram/ml unlabeled reaction extremely rapid, reaching equilibrium within 5 s either 0 C 37 Approximately 20% microvessels resistant acid wash represented internalized In addition, endothelial cytoskeleton remaining after 1% Triton X-100 extraction peptide-cytoskeletal [Tyr11]SRIF, but it inhibited 0.5% polylysine 0.8 M KCl stimulated mM dithiothreiotol. These suggest sequester degrade this represent one mechanism rapid inactivation neuropeptides subsequent neurosecretion.