To explore the potential involvement of neurotrophins in the actions of retinoic acid (RA) on leukaemia differentiation, we examined the ability of RA to regulate the expression of neurotrophins and Trk receptors in several leukaemia cell lines. Expression of TrkA was dramatically induced by RA at both the mRNA and protein level in leukaemia cell lines K562 and KG-1. Furthermore, while no expression of trkB and trkC was detected, constitutive expression of nerve growth factor (NGF), neurotrophin-3 and neurotrophin-4/5 could be detected in leukemia cells. Our findings suggested that NGF/trkA may potentially be involved in the RA-induced differentiation of leukemia cells.

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SUMMARY1. Slowly adapting type I (s.a. I) cutaneous mechanoreceptors were studied in young (3-4 months old) and adult (9-11 months old) rats. Trains of thirty repetitive mechanical stimuli with 0-1 s rise time, 1-9 s plateau phase, and 0-7 s interstimulus interval were applied. A feed-back mechanism maintained the force of stimulation at 20 mN during the plateau phases of stimuli and the contact force between stimuli at 0-5 mN.2. During the first few stimuli in a train residual indentation at contact force increased rapidly. Maximal indentation required to maintain the force of stimulation of 20 mN increased as well but to a smaller extent. Thus, the stroke amplitudes of individual stimuli decreased with increasing stimulus number.3. All displacement values in the group of adult rats were consistently reduced to 62+3 % of the respective values in the group of young rats, indicating a linear decrease in skin compliance in the force range of 0-5-20 mN. 4. Nervous responses to individual stimuli decreased from about 200 impulses for stimulus number 1 to about 60 impulses for stimulus number 30. Significant differences in the number of impulses between young and adult rats were observed from stimulus number 9 to number 16 only.5. It is concluded that the design of the s.a. I receptor allows maintained high tactile sensitivity in response to force-related stimuli irrespective of age-induced changes in mechanical properties of the skin and underlying tissues.