Redundant Gs-coupled serotonin receptors regulate amyloid-β metabolism in vivo

Table 1 Pharmacological agents used for reverse microdialysis

Compound	Target	IC₅₀ or K_i	Rev MD Concentration	Dosage Across MD Membrane	Selectivity Limit	Reference
Agonists
Ipsapirone	5-HT_1AR	10 nM	1 μM	100 nM	58 nM^a	[59]
WAY161503	5-HT_2CR	4 nM	400 nM	40 nM	233 nM	[60]
ML10302	5-HT₄R	4 nM	400 nM	40 nM	700 nM	[61]
ST1936	5-HT₆R	13 nM	1.3 μM	130 nM	168 nM	[62]
AS19	5-HT₇R	0.83 nM	83 nM	8.3 nM	6.6 nM^b	[63]
Antagonists
GR113808	5-HT₄R	0.02 nM	100 nM	10 nM	10 μM	[64]
SB258719	5-HT₇R	31.6 nM	3.16 μM	316 nM	316 nM	[68]
Inhibitors
GM6001	ADAM/MMP	0.5 nM-27 nM	2.5 μM	250 nM	NA	[66]
KT5720	PKA	60 nM	6 μM	600 nM	2 μM	[67]
PKI14-22	PKA	36 nM	3.6 μM	360 nM	15 μM	[65]

All agents were chosen for their selectivity for their targets as assayed in previous literature. We used the K_i and IC₅₀ values to determine necessary concentrations of each compound (reverse microdialysis (Rev MD) concentration). We assumed only 10 % of the drug would cross the membrane (Dosage Across MD membrane), and this amount of the compound would be further diluted in the brain ISF. The selectivity limit is the concentration above which each compound begins stimulating off-target receptors
^aIpsapirone has been shown to stimulate bovine α-adrenergic receptors at 58 nM in vitro [59]
^bAS19 can stimulate 5-HT_1DR at 6.6 nM concentrations in vitro [63]. However, expression of this receptor is absent in adult mouse hippocampus [14], so effects of its stimulation should be neglible
Abbreviations: 5-HTR serotonin receptor, ADAM a disintegrin and metallopeptidase domain, MMP matrix metallopeptidase, PKA protein kinase A

ISSN: 1750-1326