Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autologous monocytes irreversibly suppressed functions of human natural killer (NK) cells including baseline and lymphokine-induced cytotoxicity, antibody-dependent cellular cytotoxicity (ADCC), and interleukin-2 (IL-2)-induced proliferation. The suppression of these NK-cell functions was cell contact-dependent and could be evoked only by purified monocytes, recovered directly from peripheral blood by countercurrent centrifugal elutriation (CCE). The presence of monocytes also induced the disappearance of CD16 and CD56 antigen on CD3- NK cells (CD3-/16+/56+-->CD3-/16-/56-). By contrast, T-cell proliferation and the expression of CD3 on CD56- T cells were not susceptible to cell contact-mediated suppression by monocytes. The biogenic amine serotonin abrogated monocyte-induced suppression of NK-cell functions as well as down-modulation of CD16/56 NK-cell antigen. Serotonin thus markedly augmented baseline and lymphokine-induced NK-cell cytotoxicity, ADCC, and NK-cell proliferation, and maintained the expression of NK-cell surface antigens in the presence of elutriated monocytes. The effect of serotonin was mediated by 5-HT1A-type serotonin receptors (5-HT1AR) as indicated by mimicry exerted by 5-HT1AR agonists such as 8-OH-DPAT and (+)-ALK, partial antagonism by the 5-HT1AR antagonists pindolol and cyproheptadine, and lack of antagonism by the 5-HT2R antagonist ketanserin or the 5-HT3R antagonist ondansetron. Our data are suggestive of a cell-to-cell-mediated mechanism by which monocytes down-modulate NK-cell function and phenotype and its serotonergic regulation.
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PMID:Serotonergic 5-HT1A receptors regulate a cell contact-mediated interaction between natural killer cells and monocytes. 767 81

The ability of a series of compounds to mimic the stimulus properties of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was compared to: (1) the affinity of these compounds for the 5-HT1A receptor; and (2) their efficacy to inhibit forskolin-stimulated adenylate cyclase activity. Although for nine compounds (flesinoxan, MDL 73005EF, gepirone, ipsapirone, buspirone, tandospirone, yohimbine, L 657,743 and rauwolscine) complete cross generalization was associated with high affinity for the 5-HT1A receptor, eltoprazine, d-lysergic acid diethylamide and BMY 7378 had pKD > 7.44, but did not show complete mimicry of 8-OH-DPAT. In addition, indorenate had a pKD of 7.88, yet the behavioral response was indistinguishable from the saline control. Because the above data indicated that affinity for the 5-HT1A receptor was necessary, but not sufficient for a receptor ligand to mimic 8-OH-DPAT, the in vitro efficacy of the various compounds at the 5-HT1A receptor was determined by measuring inhibition of forskolin-stimulated adenylate cyclase activity in hippocampal membranes. For a series of drugs (gepirone, ipsapirone, flesinoxan, buspirone, tandospirone, yohimbine, L 657,743 and rauwolscine) significant inhibition of forskolin-stimulated adenylate cyclase activity was observed, and these same drugs showed complete cross generalization. However, BMY 14802 and MDL 73005EF did not alter adenylate cyclase activity, yet completely mimicked the stimulus properties of 8-OH-DPAT. Eltoprazine had significant efficacy in inhibiting forskolin-stimulated adenylate cyclase activity, but only 30% of the responses following administration of this drug were on the 8-OH-DPAT-appropriate lever. Furthermore, although indorenate inhibited hippocampal adenylate cyclase activity, the behavioral response to this compound was indistinguishable from the saline control.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Studies of the biochemical basis for the discriminative properties of 8-hydroxy-2-(di-n-propylamino)tetralin. 850 5