Activation of the dopamine- and cAMP-regulated phosphoprotein of Mr 32 kDa (DARPP-32) intracellular cascade mediates responses to cocaine.
To examine the possibility that acute cocaine administration alters the DARPP-32 cascade in a sexually dimorphic pattern.
Male and Z-IETD-FMK clinical trial female rats received either saline or cocaine (30 mg/kg). Protein levels of DARPP-32, phosphorylation of DARPP-32 at the Thr34 site (P-Thr34-DARPP-32), protein phosphatase 1 (PP-1), and protein phosphatase 2B (PP-2B) in nucleus accumbens were measured via
Western blot analysis.
Females had higher protein levels of DARPP-32, P-Thr34-DARPP-32, calcineurin A (CaN-A; catalytic subunit of PP-2B), and calcineurin B (CaN-B; regulatory subunit of PP-2B) than males 5 min after saline treatment. In females, CaN-A protein levels were also higher at 15 min and PP-1 protein levels were higher 30 min after saline administration than males. In male rats, cocaine significantly increased CaN-A protein levels at 30 min and CaN-B protein levels at 15 min. In females, cocaine administration significantly decreased protein levels of DARPP-32, P-Thr34-DARPP-32,
and CaN-A at 45 min but increased PP-1 protein levels at 30 min. Overall, males had higher activation of the DARPP-32 pathway after cocaine administration than did females.
These novel results show that basal and cocaine-induced sex differences in the DARPP-32/PP-1 cascade may be responsible for the sexual dimorphism in acute cocaine-induced behavioral responses.”
“Objective: Tc-99m-Sn-PYP (Technetium-99(m) labeled tin pyrophosphate) has Selleckchem Pitavastatin been widely used as a radiopharmaceutical for bone scanning as well as in nuclear cardiology. It is also found in the body in trace amounts. Lu-177 is presently considered as an excellent radionuclide for developing bone pain palliation agents. PYP is an analogue of MDP and MDP has been labeled with Lu-177. No study on preparing a complex of Lu-177 with PYP has been reported yet. Based on these facts, it was hypothesized that a bone-seeking Celastrol Lu-177-PYP (Lutetium-177 labeled Pyrophosphate) radiopharmaceutical could be developed as
an agent for palliative radiotherapy of bone pain due to skeletal metastases.
Methods: Lu-177 was produced by irradiating lutetium foil (11 mg) natural target at a flux similar to 1.0 x 10(14)n/cm(2)/s for 12 h in the swimming pool type reactor. Lu-177 in the form of (LuCl3)-Lu-177 was labeled with PYP. The radiochemical purity and labeling efficiencies were determined by paper chromatography. Labeling of Lu-177 with PYP was optimized and a labeled sample was subjected to HPLC analysis. To determine the charge on the Lu-177-PYP complex, radio-electrophoresis was conducted for 1 h under a voltage of 300 V and 45 mA current using 0.025 M phosphate buffer (pH 6.9). Bioevaluation studies with rabbit under gamma-camera were also performed to verify the skeletal uptake.