In:
European Journal of Biochemistry, Wiley, Vol. 249, No. 2 ( 1997-10), p. 547-555
Abstract:
In single platelets and in suspensions of platelets, α‐thrombin evokes dose‐dependent, transient increases in cytosolic Ca 2+ concentration, [Ca 2+ ] ij , which are more prolonged than the [Ca 2+ ]; transients evoked by other platelet agonists such as the thrombin‐receptor‐activating hexapeptide SFLLRN, thromboxane A 2 analog U46619, and ADP As a quantity taking into account both the magnitude and length of the Ca 2+ response, we defined the Ca 2+ ‐mobilizing potency (CMP) of an agonist as the integrated rise in [Ca 2+ ] i during the time of the Ca 2+ signal. It was observed that: (a) the CMP increased with the agonist concentration in a saturating way, its maximal value being about four‐times higher with α‐thrombin than with SFLLRN; (b) the high CMP of α‐thrombin was for only a small part due to endogenous production of ADP or thromboxane, and was mainly a consequence of prolonged influx of external Ca 2+ ; (c) the CMP declined when a‐thrombin was inactivated during the course of the Ca 2+ signal; (d) CMP values increased with the agonist concentration upon sequential addition of increasing amounts of α‐thrombin or SFLLRN; (e) when α‐thrombin was gradually added to the platelets or formed by an in situ reconstituted prothrombinase system (with factor Xa, factor Va, and prothrombin), integrated Ca 2+ responses were a function of the product of the α‐thrombin concentration and the time of its presence. However, in these cases, the final CMP values were independent of the rate of α‐thrombin addition or formation. We conclude that α‐thrombin‐induced Ca 2+ signals in platelets rely largely upon Ca 2+ influx, are not, or only slightly, subjected to homologous desensitization, and reflect the enzymatic capacity of α‐thrombin to cleave protease‐activated receptors. Thus, the high and prolonged Ca 2+ signal induced by α‐thrombin is due to continuous receptor cleavage without desensitizing effects of previously cleaved receptors.
Type of Medium:
Online Resource
ISSN:
0014-2956
,
1432-1033
DOI:
10.1111/ejb.1997.249.issue-2
DOI:
10.1111/j.1432-1033.1997.00547.x
Language:
English
Publisher:
Wiley
Publication Date:
1997
detail.hit.zdb_id:
1398347-7
detail.hit.zdb_id:
2172518-4
SSG:
12
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