Defective Serotonin (5‐HT) Transport Mechanism in Platelets from Patients with Endogenous and Allergic Asthma

Abstract

The kinetics of the 5-HT-uptake by platelets in platelet-rich plasma (PRP) and PRP diluted with autologous platelet-poor plasma (PRP/PPP) were determined in normal subjects, patients with asymptomatic exogenous asthma and those with symptomatic endogenous asthma.In normal subjects the 5-HT-uptake by platelets strictly obeyed Michaelis-Menten's kinetics. In patients with asymptomatic exogenous asthma, the active 5-HT-transport was moderately distorted in PRP and severely altered in PRP/PPP. Patients with symptomatic endogenous asthma exhibited already in PRP a dramatic transport disturbance.The alteration of the active 5-HT-transport was characterized by increasing uptake inhibition by rising 5-HT concentrations in plasma. This phenomenon could be due to changes in the platelet environment, defects in the platelet membrane or intrinsic platelet disorders. It is concluded that asthmatics have a genetically or later acquired platelet disorder, which is more clearly observed in patients with symptomatic endogenous asthma than in those with asymptomatic exogenous asthma.Kcy words: endogenous and exogenous asthmatics; platelets; serotonin transport. Accepted for publicdon 22 August 1981 CLINICAL ASPECTSThe 5-€IT (serotonia) uptake by platelets from patients with nstbma WPB studied. J n patients with symptomatic endogenous nsthma, the 5-HT-uptake by platelets WM severely impaired, and aUghtly disturbed in platelets from patients with psymptomntic exogenous M -.Serum and whole blood from asthmatic patients haa proved to contain higher amounts of 5-HT than that of normal subjects, and elevated levels of 5-HT-metaboliterr ouch M kynureniae has been demonstrated in such patients. Furthermore, tryptophan load on psthmaties leads to abnormally higb urinary excretion of xnnthurenic acid.As tryptophan ia the main precursor in 5-HT synthesis, a reduced tryptophan intake might thus be of importance.It is reported that patients with allergic asthma have higher blood levels of 5-HT than normal persons (3, 9) and excrete more 5-HT metabolites in urine (21). Asthmatic patients also seem to be more sensitive to administration of 5-HT than healthy subjects (4). Since the circulating platelet is involved in the uptake, secretion, and transport of 5-HT (15), we have previously found reason to study platelets from asthmatic patients. It was demonstrated that such platelets have a reduced capacity to accumulate 5-HT (11) and a disturbed active 5-HT uptake mechanism (12).The experimental conditions, under which the 5-HT binding and uptake by platelets should be performed, have been further elaborated, as has the mathematical treatment of data for detecting abnormalities in kinetic pat-0 1054538/82/0 1002%l1 $02.50/0 0 1982 Munksgaard, Copenhagen

The effects of 5‐HT on cholinergic contraction in human airways in vitro

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