Plasma chromogranin A: a marker of serotonin release and of emesis associated with cisplatin chemotherapy.
OBJECTIVE
Emesis is a common side effect of cancer chemotherapy. Serotonin released from gastrointestinal enterochromaffin cells (ECC) may mediate chemotherapy-induced emesis. Since chromogranin A (CgA) is colocalized in ECC storage granules with serotonin, we tested the hypothesis that plasma CgA could mark emesis and serotonin release from ECC.


METHODS
The relationships between plasma CgA, serotonin release, and the development of vomiting following the first course of cisplatin chemotherapy were evaluated in 60 patients.


RESULTS
CgA levels increased in 59 of 60 patients (245% +/- 18% increase above baseline levels, P < .001). The time course of the increase in plasma CgA matched that of emesis and of urinary 5-hydroxyindoleacetic acid (5-HIAA). Significant (P < .001) positive correlations were found between the dose of cisplatin and the increases in plasma CgA, and between the changes in plasma CgA and urinary 5-HIAA after cisplatin (r = .54, n = 39, P < .001). The increase in plasma CgA after cisplatin did not correlate with changes in serum lactic dehydrogenase (LDH) activity, a marker of cell toxicity or lysis.


CONCLUSIONS
Plasma CgA marks emesis and serotonin release induced by cisplatin. Since both CgA and serotonin are costored in ECC granules, we suggest that the source of release of each may be the ECC. Increases in plasma CgA are not explained by drug cytotoxicity. Exocytosis appears as the main mechanism by which cisplatin releases serotonin. This work further supports the role of serotonin as a mediator of emesis associated with cisplatin and suggests that plasma CgA level is a valuable tool in studies of chemotherapy-induced emesis.
Cubeddu
L X
LX
Department of Pharmacology, School of Pharmacy, Central University of Venezuela, Caracas.
O'Connor
D T
DT
Parmer
R J
RJ
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D053379:Chromogranin A; D002864:Chromogranins / Q000097:blood*; D002945:Cisplatin / Q000009:adverse effects*; D004759:Enterochromaffin Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000652:urine; D007770:L-Lactate Dehydrogenase / Q000097:blood; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012701:Serotonin / Q000378:metabolism*; D014839:Vomiting / Q000139:chemically induced* / Q000378:metabolism
C506150:CHGA protein, human; D053379:Chromogranin A; D002864:Chromogranins; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D007770:L-Lactate Dehydrogenase; D002945:Cisplatin