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)

Corticosteroids influence neuron activity in the hippocampus through the activation of mineralocorticoid and glucocorticoid receptors. For example, corticosteroids modulate the responses elicited by the activation of several different neurotransmitter receptors on hippocampal pyramidal cells. However, the effects of corticosteroids on the serotonin (5-HT) receptors systems in subfield CA3 are not completely known. Therefore, we used single-electrode voltage clamp techniques to examine the actions of chronic corticosteroid treatment on the 5-HT1A receptor-effector pathway in rat hippocampal subfield CA3 pyramidal cells. Activation of the 5-HT1A receptor increases the conductance of an inward rectifying potassium channel, increasing outward current. The treatment groups used in this investigation were: adrenalectomy, selective mineralcorticoid receptor activation with aldosterone, mineralcorticoid receptor and glucocorticoid receptor activation with high levels of corticosterone and SHAM. Corticosteroids altered the characteristics of the 5-HT concentration-response curve for the 5-HT1A receptor. The effective concentration at 50% of maximum value was smaller in cells from the adrenalectomy treatment group compared to the other treatment groups. The maximum response was smaller in cells from the high corticosterone treatment group compared to SHAM and adrenalectomy treatment group animals. G protein function was also altered by corticosterone treatment. Less current was elicited by guanosine 5'-0-13-thiotriphosphate in cells from the high corticosterone treatment group compared to the other treatment groups and in cells from the SHAM treatment group compared to adrenalectomy treatment group animals. Corticosteroid treatment did not alter the current-voltage relationship, the conductance or the reversal potential of the potassium current linked to the 5-HT1A receptor. We conclude that corticosteroids alter the 5-HT1A receptor-mediated-response in hippocampal subfield CA3 neurons at site(s) downstream of the receptor.
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PMID:Corticosteroids alter 5-hydroxytryptamine1A receptor-effector pathway in hippocampal subfield CA3 pyramidal cells. 949 87

The inwardly rectifying K+ (Kir) channel Kir4.1 is responsible for astroglial K+ buffering. We recently found that tricyclic antidepressants (TCAs) inhibit Kir4.1 channel currents, which suggests that astroglial Kir currents might be involved in the pharmacological action of antidepressants. We therefore further examined the effects of the currently most popular antidepressants, selective serotonin reuptake inhibitors (SSRIs), and other related agents on Kir4.1 channels heterologously expressed in HEK293T cells. The whole-cell patch clamp technique was used. Fluoxetine, the typical SSRI, inhibited Kir4.1 channel currents in a concentration-dependent manner with an IC50 value of 15.2 microM. The inhibitory effect of fluoxetine was reversible and essentially voltage-independent. Fluoxetine had little or no effect upon Kir1.1 (ROMK1) or Kir2.1 (IRK1) channel currents. Other SSRIs, sertraline and fluvoxamine, also inhibited Kir4.1 channel currents whereas the tetracyclic (mianserin) or the 5-HT1A receptor-related (buspirone) antidepressants did not. This study shows that SSRIs such as fluoxetine and sertraline preferentially block astroglial Kir4.1 rather than Kir1.1 or Kir2.1 channels in the brain, which may be implicated in their therapeutic and/or adverse actions.
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PMID:Inhibition of astroglial Kir4.1 channels by selective serotonin reuptake inhibitors. 1792 44