While much initial focus has been on the 5-HT1A autoreceptors, it seems 5-HT(5A)R's are also autoreceptors, and interexchangeable signaling projectors. That is , they modulate homeostasis in the serotonergic systems, and when they are activated, they downregulate the 5-HT1A autoreceptor or decrease it's function, which makes sense....activate one* autoreceptor, brain downregulates another to compensate for the decrease in serotonin.
THUS, serotonin may be a more "radical" neurotransmitter than we have previously thought, with a whopping 5 autoreceptors to count; unprecedented!
http://www.jneurosci.org/content/32/17/5804.full.pdf
THUS, serotonin may be a more "radical" neurotransmitter than we have previously thought, with a whopping 5 autoreceptors to count; unprecedented!
http://www.jneurosci.org/content/32/17/5804.full.pdf
The 5-HT5A receptor is the least understood serotonin (5-HT) receptor. Here, we electrophysiologically identify and characterize a native 5-HT5A receptor current in acute ex vivo brain slices of adult rodent prefrontal cortex. In the presence of antagonists for the previously characterized 5-HT1A and 5-HT2 receptors, a proportion of layer V pyramidal neurons continue to show 5-HT-elicited outward currents in both rats and mice. These 5-HT currents are suppressed by the selective 5-HT5A antagonist, SB-699551, and are not observed in 5-HT5A
receptor knock-out mice. Further characterization reveals that the 5-HT5A current is activated by submicromolar concentrations of 5-HT,
is inwardly rectifying with a reversal potential near the equilibrium potential for K ions, and is suppressed by blockers of Kir3 channels.
Finally, we observe that genetic deletion of the inhibitory 5-HT5A receptor results in an unexpected, large increase in the inhibitory 5-HT1A receptor currents. The presence of functional prefrontal 5-HT5A receptors in normal rodents along with compensatory plasticity in 5-HT5A receptor knock-out mice testifies to the significance of this receptor in the healthy prefrontal cortex.
