Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The fibrinolytic enzyme plasmin at 0.25 units/ml produced a contraction of isolated canine basilar arteries that developed slowly and was sustained for at least 2 hours. Plasmin and thrombin (1 unit/ml) acted synergistically to enhance the contractile response. In contrast to plasmin, the marked contraction elicited by thrombin ended within 1 hour, and afterward the artery was completely tachyphylactic to thrombin. Fibrin clot, fibrinopeptides, and fibrin degradation products did not prolong significantly the effect of thrombin or prevent the tachyphylaxis. Plasmin and thrombin may occupy a common membrane receptor because exposing the artery briefly to trypsin (24 micrograms/ml) thereafter abolished the contractile effect of plasmin and thrombin without affecting the action of other agonists. Antithrombin III (1.0 unit/ml) relaxed basilar arteries that were precontracted with plasmin (0.5 unit/ml), thrombin (1.0 unit/ml), serotonin (10(-5) M), uridine triphosphate (10(-4) M), or KCl (8 X 10(-2) M). The results suggest that the vasoconstrictor effect of thrombin might contribute to hemostasis after subarachnoid hemorrhage (SAH) but, because of tachyphylaxis, not to delayed vasospasm. On the other hand, the constrictor action of plasmin might appear late in the course of SAH in association with clot lysis and tissue repair. Last, the level of the vasorelaxant antithrombin III in cerebrospinal fluid could control the appearance and severity of cerebral arterial spasm in SAH.
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PMID:Role of plasmin, thrombin, and antithrombin III as etiological factors in delayed cerebral vasospasm. 257 47

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