Age-related Changes in 5-HT2 Serotonin Receptor on Human Platelets

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Chanchira Limthavon
Anan Srikiatkhachorn
Piyarat Govitrapong

Abstract

Numerous studies suggest that serotonergic nervous system may be involved in the neurophysiological processes in age-related learning and memory. A reduction in biochemical markers of serotonergic synapses also has been reported. Besides the central nervous system, 5-hydroxytryptamine (5-HT) is also found in blood platelets. Platelets and serotonergic nerve endings share many morphological, biochemical and pharmacological characteristics. The present experiment is performed by using platelet as a model for 5-HT neuron activity. By using radioligand binding technique, 5-HT2 serotonin receptor subtype has been identified and characterized in human platelet membrane. [3HJ-spiperone in various concentrations (0.2-

10 nM) used as radioligand whereas ketanserin, a selective 5-HT2 serotonin antagonist was used to determine the non-specific binding. The association binding was reached to equilibrium within 30 min and remained constant for at least two hr. The saturation experiment revealed a single binding site with a dissociation equilibrium constant (Kd) of 3.41±0.95 nM and a receptor density (Bmax) of 86.59 ± 9.09 f mol/mg protein. Several drugs were used to compete with [3H]-spiperone binding having the descending order of potency: ritanseriroprazosin >pipamperone >pirenperone >ketanserin >spiperone > methysergide > chlorpromazine > haloperidol > sulpiride >serotonin> imipramine. The results indicate that human platelets contain 5-HT2 serotonin receptor binding. The Bmax value of the elderly is significantly reduced when compared with young adult subjects (39.96 ± 5.42 f mol/mg protein, 86.59 ± 9.09 f mol/mg protein, respectively), whereas the Kd value is non-significant different between these two groups, elderly healthy and young adult subjects, (2.84 ± 0.48 and 3.41±0.95 nM respectively).

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Research Articles