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Home / Equine Research Bank / Am J Pathol / Modulation of equine platelet function by diethylcarbamazine...
The American journal of pathology1983; 113(1); 1-7;

Modulation of equine platelet function by diethylcarbamazine (DEC).

Abstract: Equine platelets, when treated with the anthelmintic drug diethylcarbamazine (DEC), gave a dose-dependent release of radiolabeled serotonin without concomitant aggregation. At levels of the drug that gave only minimal release of radiolabel, marked dose-dependent inhibition of platelet aggregation to three of four platelet agonists tested--adenosine diphosphate (ADP), collagen, and arachidonic acid--was observed. With ADP, inhibition was observed to be reversed by removal of DEC prior to agonist challenge. However, with collagen, inhibition was only partially reduced by prior removal of DEC; whereas with arachidonate the DEC inhibition appeared not to be reduced by removal of the drug. Thrombin-induced aggregation was not inhibited by DEC. DEC therefore has the heretofore unrecognized property of modulating platelet function to several platelet agonists as well as inducing the platelet release of serotonin. Our results would suggest a reversible membrane-drug interaction as the potential site of modulation for ADP and collagen, whereas an apparent irreversible inhibition is suggested for arachidonate-induced aggregation.
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Publication Date: 1983-10-01 PubMed ID: 6414306PubMed Central: PMC1916298
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  • Journal Article
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  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study explains how the anthelmintic drug diethylcarbamazine (DEC) affects the function of horse platelets. Specifically, it details how the drug causes a dose-dependent release of serotonin and inhibits platelet aggregation in response to various platelet agonists.

DEC Effects on Serotonin Release and Platelet Aggregation

  • DEC, an anthelmintic drug, was observed to cause a dose-dependent release of radiolabeled serotonin from equine platelets. This means that as the dosage of DEC increased, so did the release of serotonin.
  • This release of serotonin did not coincide with platelet aggregation, the process where blood cells clump together. This was an important observation as serotonin release typically accompanies platelet aggregation.

Inhibition of Platelet Aggregation by DEC

  • The study looked at the effects of DEC on platelet aggregation caused by several platelet agonists, including adenosine diphosphate (ADP), collagen, arachidonic acid, and thrombin.
  • With low-level DEC use that only minimally prompted serotonin release, the research identified significant dose-dependent inhibition of platelet aggregation for three of four platelet agonists tested: ADP, collagen, and arachidonic acid.
  • This means the drug was able to suppress the aggregation prompted by these substances in a dose-dependent manner; the higher the DEC dosage, the greater the inhibition.
  • In contrast, Thrombin-induced aggregation was not inhibited by DEC

Reversibility of DEC Inhibition

  • The study observed different degrees of reversibility for DEC’s inhibition of aggregation based on the specific platelet agonist tested.
  • With ADP, inhibition was fully reversed when DEC was removed before presenting the agonist. This suggests that the interaction between DEC and the platelets’ membrane might be at the center of the observed modulation.
  • With collagen, on the other hand, the removal of DEC only led to a partial reduction of the inhibition.
  • Most strikingly, the inhibition that occurred in response to arachidonate was seemingly irreversible, as it persisted even after the removal of DEC.

Significance of the Findings

  • This study demonstrates that DEC has previously unrecognized capabilities of altering platelet function.
  • The differences in the reversibility of DEC’s effects hint at the possibility of multiple mechanisms of action, depending on the specific platelet agonist involved.

Cite This Article

APA
Kowalski KA, McConnell LA, Sadoff DA, Leid RW. (1983). Modulation of equine platelet function by diethylcarbamazine (DEC). Am J Pathol, 113(1), 1-7.

Publication

The American journal of pathology
ISSN: 0002-9440
NlmUniqueID: 0370502
Country: United States
Language: English
Volume: 113
Issue: 1
Pages: 1-7

Researcher Affiliations

Kowalski, K A
    McConnell, L A
      Sadoff, D A
        Leid, R W

          MeSH Terms

          • Adenosine Diphosphate / pharmacology
          • Animals
          • Arachidonic Acid
          • Arachidonic Acids / pharmacology
          • Collagen / pharmacology
          • Depression, Chemical
          • Diethylcarbamazine / pharmacology
          • Horses
          • Platelet Aggregation / drug effects
          • Serotonin / blood
          • Thrombin / pharmacology

          References

          This article includes 19 references
          1. O'Brien JR. Effects of salicylates on human platelets.. Lancet 1968 Apr 13;1(7546):779-83.
            pubmed: 4171129doi: 10.1016/s0140-6736(68)92228-9google scholar: lookup
          2. Zucker MB, Peterson J. Inhibition of adenosine diphosphate-induced secondary aggregation and other platelet functions by acetylsalicylic acid ingestion.. Proc Soc Exp Biol Med 1968 Feb;127(2):547-51.
            pubmed: 5645047doi: 10.3181/00379727-127-32737google scholar: lookup
          3. Orange RP, Austen KF. Drug-induced modulation of the immunologic release of histamine and slow reacting substance of anaphylaxis.. Int Arch Allergy Appl Immunol 1971;41(1):79-85.
            pubmed: 4104672doi: 10.1159/000230490google scholar: lookup
          4. Smith JB, Willis AL. Aspirin selectively inhibits prostaglandin production in human platelets.. Nat New Biol 1971 Jun 23;231(25):235-7.
            pubmed: 5284361doi: 10.1038/newbio231235a0google scholar: lookup
          5. Duke BO, Vincelette J, Moore PJ. Microfilariae in the cerebrospinal fluid, and neurological complications, during treatment of onchocerciasis with diethylcarbamazine.. Tropenmed Parasitol 1976 Jun;27(2):123-32.
            pubmed: 941247
          6. Duke BO, Vincelette J, Moore PJ. The populatin dynamics of Onchocerca volvulus microfilariae during treatment with suramin and diethylcarbamazine.. Tropenmed Parasitol 1976 Jun;27(2):133-44.
            pubmed: 941248
          7. Anderson J, Fuglsang H, de C Marshall TF. Effects of diethylcarbamazine on ocular onchocerciasis.. Tropenmed Parasitol 1976 Sep;27(3):263-78.
            pubmed: 982546
          8. Anderson J, Fuglsang H, de C Marshall TF. Effects of suramin on ocular onchocerciasis.. Tropenmed Parasitol 1976 Sep;27(3):279-96.
            pubmed: 982547
          9. Anderson J, Fuglsang H. Ocular onchocerciasis.. Trop Dis Bull 1977 Apr;74(4):257-72.
            pubmed: 329507
          10. Kinlough-Rathbone RL, Packham MA, Mustard JF. Synergism between platelet aggregating agents: the role of the arachidonate pathway.. Thromb Res 1977 Nov;11(5):567-80.
            pubmed: 337565doi: 10.1016/0049-3848(77)90016-0google scholar: lookup
          11. Connor DH. Onchocerciasis.. N Engl J Med 1978 Feb 16;298(7):379-81.
            pubmed: 622107doi: 10.1056/NEJM197802162980706google scholar: lookup
          12. Rée GH, Hall AP, Hutchinson DB, Weatherley BC. Plasma levels of diethylcarbamazine in man.. Trans R Soc Trop Med Hyg 1977;71(6):542-3.
            pubmed: 605466doi: 10.1016/0035-9203(77)90151-1google scholar: lookup
          13. Gibson DW, Connor DH. Onchocercal lymphadenitis: Clinicopathologic study of 34 patients.. Trans R Soc Trop Med Hyg 1978;72(2):137-54.
            pubmed: 653785doi: 10.1016/0035-9203(78)90049-4google scholar: lookup
          14. Jones BR, Anderson J, Fuglsang H. Effects of various concentrations of diethylcarbamazine citrate applied as eye drops in ocular onchocerciasis, and the possibilities of improved therapy from continuous non-pulsed delivery.. Br J Ophthalmol 1978 Jul;62(7):428-39.
            pubmed: 678494doi: 10.1136/bjo.62.7.428google scholar: lookup
          15. Anderson J, Fuglsang H. Further studies on the treatment of ocular onchocerciasis with diethylcarbamazine and suramin.. Br J Ophthalmol 1978 Jul;62(7):450-7.
            pubmed: 678497doi: 10.1136/bjo.62.7.450google scholar: lookup
          16. Taylor HR, Greene BM, Langham ME. Controlled clinical trial of oral and topical diethylcarbamazine in treatment of onchocerciasis.. Lancet 1980 May 3;1(8175):943-6.
            pubmed: 6103299doi: 10.1016/s0140-6736(80)91402-6google scholar: lookup
          17. Vargaftig BB, Chignard M, Le Couedic JP, Benveniste J. One, two, three or more pathways for platelet aggregation.. Acta Med Scand Suppl 1980;642:23-9.
            pubmed: 6779505doi: 10.1111/j.0954-6820.1980.tb10931.xgoogle scholar: lookup
          18. Piper PJ, Temple DM. The effect of lipoxygenase inhibitors and diethylcarbamazine on the immunological release of slow reacting substance of anaphylaxis (SRS-A) from guinea-pig chopped lung.. J Pharm Pharmacol 1981 Jun;33(6):384-6.
            pubmed: 6115013doi: 10.1111/j.2042-7158.1981.tb13810.xgoogle scholar: lookup
          19. Mathews WR, Murphy RC. Inhibition of leukotriene biosynthesis in mastocytoma cells by diethylcarbamazine.. Biochem Pharmacol 1982 Jun 1;31(11):2129-32.
            pubmed: 6288051doi: 10.1016/0006-2952(82)90435-xgoogle scholar: lookup

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