SQ22536

Biological Activity

In vitro: SQ22536(250 µmol/L) attenuates the inhibitory effect of adenosine against ADP-induced platelet aggregation from 8±5 to 57±5%, respectively (p<0.001). SQ22536 also attenuates an increase of intraplatelet levels of cAMP by adenosine from 29±2 to 9±1 pmol/108 platelets (p<0.05). It has no effect on the platelet antiaggregant activity of inosine (1 to 4 mmol/L) and ADP-induced platelet aggregation. In vivo: SQ22536 abolishes the renal protective effects of liraglutide in KK/Ta-Akita mice. the amelioration of glomerular histopathological damage by liraglutide is eliminated in KK/Ta-Akita mice treated with liraglutide in combination with SQ22536. Renal cAMP does not increase after treatment with SQ22536. In a word, the beneficial actions of liraglutide for treatment of nephropathy are inhibited by the adenylate cyclase inhibitor SQ22536.

Protocol

Cell Experiment
Cell lines	Human leukemic mast cell line(HMC-1) and human umbilical cord blood-derived mast cell(hCBMCs)
Preparation method	HMC-1 cells and hCBMCs are plated in 48-well plates and serum-starved overnight. The next day, cells are preincubated with SQ22536 at the indicated concentrations for 30 min before stimulation with CRH (100 nM for HMC-1 or 1 μM for hCBMC) for 3 min in the presence or absence of SQ22536 in serum-free culture media. Cell lysates are then prepared and assayed for protein kinase A activity using ELISA.
Concentrations	0.1, 1, 10 mM
Incubation time	30 min

Animal Experiment
Animal models	Male C57BL/6J mice
Formulation	Saline
Dosages	10 mg/kg
Administration	s.c.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information

References

The vasopressin type 2 receptor and prostaglandin receptors EP2 and EP4 can increase aquaporin-2 plasma membrane targeting through a cAMP-independent pathway.
Olesen ET, et al. Am J Physiol Renal Physiol. 2016 Nov 1;311(5):F935-F944. PMID: 27558562.

The role of adenylyl cyclase in the medial prefrontal cortex in cocaine-induced behavioral sensitization in rats.
Liu K, et al. Neuropharmacology. 2016 Dec;111:70-77. PMID: 27020043.