Serotonin stimulation of calcium mobilisation in human platelets: choice of units of measurement, effects of age and tobacco use, and correlation with serotonin2A receptor density.
The calcium responses to serotonin and thrombin, as assessed using the fluorescent indicator Fura-2, have been investigated in platelets taken from 59 non-smokers and 17 smokers. The peak responses above baseline, calculated either as fluorescence ratios or calibrated calcium concentrations, were in the order of magnitude thrombin 520 mU/ml > thrombin 52 mU/ml >> serotonin 1 micromol/l approximately serotonin 100 micromol/l. Multiple regression analyses indicated that the responses to 1 micromol/l serotonin, but not the responses to thrombin, were significantly correlated with the serotonin2A receptor density measured using [3H]LSD as radioligand. No effects of age, gender, smoking habit or the time of year of sampling were seen on the calcium responses to serotonin and thrombin. It is concluded that cellular processes distal to the serotonin2A receptor recognition site may compensate to some extent for the large differences in recognition site expression, thus underlining the importance of providing a functional correlate in addition to [3H]LSD binding site densities when studying platelet serotonin2A receptors in neuropsychiatric disorders. The measurement of Ca2+ responses to serotonin provides a useful such functional correlate.
Fowler
C J
CJ
Department of Pharmacology and Clinical Neuroscience, Umeå University, Sweden. cf@pharm.umu.se
Sjöberg
E
E
Tiger
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000375:Aging / Q000378:metabolism; D000662:Amphetamines / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D008238:Lysergic Acid Diethylamide / Q000378:metabolism; D014026:Nicotiana; D010947:Plants, Toxic; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D012907:Smoking / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013917:Thrombin / Q000494:pharmacology; D014316:Tritium; D064424:Tobacco Use
C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D000662:Amphetamines; D002118:Calcium; D008238:Lysergic Acid Diethylamide; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012701:Serotonin; D013917:Thrombin; D014316:Tritium