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)

Experiments were performed on isolated human cerebral arteries to evaluate the role desensitization and tachyphylaxis might play in preventing certain agonists from producing prolonged vasoconstriction after subarachnoid hemorrhage. In addition, the antiproteases leupeptin and pepstatin were studied to ascertain whether these peptides might inhibit contraction as does antithrombin III. The maximal contraction to KCl was used as a standard for comparing the responses elicited by the agonists, the decay of the responses to the agonists over 15 minutes was used as an index of desensitization, and the percentage of decrease in response to a second application of the agonist over the first was a measure of tachyphylaxis. The results showed that desensitization and tachyphylaxis greatly reduced or abolished the contractile responses to norepinephrine, serotonin, angiotensin II, arginine vasopressin, substance P, neuropeptide Y, neurotensin, thrombin, uridine triphosphate, linoleic acid, melittin, and cathepsin D. Moreover, some arteries failed to respond to some of these agonists, and no contractile response was elicited by acetylcholine or bradykinin. In contrast, prostaglandins E2, D2, and F2 alpha, as well as plasmin, produced sustained contractions, without tachyphylaxis, but only prostaglandin E2 and plasmin produced contractions at concentrations of 10(-7) M or less that were comparable to those of KCl. None of the antiprotease peptides inhibited the responses to KCl whereas small concentrations (6 X 10(-8) M) of antithrombin III did. The results support the hypotheses that the phenomenon of desensitization and tachyphylaxis would prevent many diverse agents from acting as spasmogens and that substances like antithrombin III present in the cerebrospinal fluid after hemorrhage could immediately protect patients from cerebral vasospasm.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacodynamic evaluation of human cerebral arteries in the genesis of vasospasm. 368 86

A pentapeptide, Ala-Arg-Pro-Ala-Lys, liberated from fibrinogen during plasmin-mediated fibrinolysis, was shown earlier to increase microvascular permeability in rat and human skin. Eighteen new analogues have now been synthesized in addition to the 15 previously prepared and examined for their effect on permeability. The old concept that a tetrapeptide with basic amino acids at both ends and a proline residue adjacent to the N-terminal amino acid is essential for high activity on permeability, has now been challenged. The results obtained with several of the new analogues strengthen this concept. More interestingly, however, the third amino acid, which was found in earlier studies to be less sensitive to exchange, has now been deleted as well as duplicated with only a modest loss of activity of the peptide. The chirality of the C-terminal amino acid, most surprisingly, does not seem to be crucial for peptide activity. Slightly superpotent analogues were obtained on amidation of the C-terminus. In addition, a few naturally occurring peptides, namely tuftsin, substance P, neurotensin and bradykinin, the amino acid sequences of which all exhibit characteristic features of some of our active peptide analogues were investigated in the same test system. Tuftsin displayed a potency equal to that of the pentapeptide. The other three peptides were all highly superpotent in this assay system.
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PMID:Structural requirements for microvascular permeability-increasing ability of peptides. Studies on analogues of a fibrinogen pentapeptide fragment. 684 82