The first druglike selective angiotensin II AT(2) receptor agonist (21) with a K(i) value of 0.4 nM for the AT(2) receptor and a K(i) > 10 microM for the AT(1) receptor is reported. Compound 21, with a bioavailability of 20-30% after oral administration and a half-life estimated to 4 h in rat, induces outgrowth of neurite cells, stimulates p42/p44(mapk), enhances in vivo duodenal alkaline secretion in Sprague-Dawley rats, and lowers the mean arterial blood pressure in anesthetized, spontaneously hypertensive rats. Thus, the peptidomimetic 21 exerts a similar biological response as the endogenous peptide angiotensin II after selective activation of the AT(2) receptor. Compound 21, derived from the prototype nonselective AT(1)/AT(2) receptor agonist L-162,313 will serve as a valuable research tool, enabling studies of the function of the AT(2) receptor in more detail.
Light absorption by aerosols is one of the most uncertain parameters associated with the direct and indirect aerosol effects on climate and is one of the most difficult quantities to measure. This article describes the development of a sensitive method of measuring aerosol absorption at 532 nm with excellent time response (detection limit: 0.08 Mm −1 , 60 second average) using photoacoustic absorption spectroscopy. An accurate calibration method (accuracy of 1-2%) at atmospherically relevant absorption levels and independent validation of the photoacoustic technique is presented. An upper limit to the instrument precision for aerosol absorption measurement is ∼6% (2σ , 30 sec) while instrument accuracy is calculated to be ∼5%. A standard for aerosol absorption measurement techniques using well characterized absorbing aerosol is also proposed.
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