ABSTRACT
We describe the cold-atom vacuum standards (CAVS) under development at the National Institute of Standards and Technology (NIST). The CAVS measures pressure in the ultra-high and extreme-high vacuum regimes by measuring the loss rate of sub-millikelvin sensor atoms from a magnetic trap. Ab initio quantum scattering calculations of cross sections and rate coefficients relate the density of background gas molecules or atoms to the loss rate of ultra-cold sensor atoms. The resulting measurement of pressure through the ideal gas law is traceable to the second and the kelvin, making it a primary realization of the pascal. At NIST, two versions of the CAVS have been constructed: a laboratory standard used to achieve the lowest possible uncertainties and pressures, and a portable version that is a potential replacement for the Bayard-Alpert ionization gauge. Both types of CAVSs are connected to a combined extreme-high vacuum flowmeter and dynamic expansion system to enable sensing of a known pressure of gas. In the near future, we anticipate being able to compare the laboratory scale CAVS, the portable CAVS, and the flowmeter/dynamic expansion system to validate the operation of the CAVS as both a standard and vacuum gauge.
ABSTRACT
To determine whether bronchoconstriction can be mediated via the tachykinin NK3 receptors, isolated guinea pig lungs were challenged with the exogenous tachykinin NK3-receptor agonists [MePhe7]-neurokinin B ([MePhe7]-NKB) and senktide. [MePhe7]-NKB induced bronchoconstriction (EC50 = 11.8 ± 1.7 µM) that was significantly inhibited by the tachykinin NK3-receptor antagonist SB 223412 at 10 µM (EC50 = 24.4 ± 4.5 µM). Senktide also induced bronchoconstriction (EC50 = 96.2 ± 20.3 µM) and the bronchoconstriction was significantly reduced by SB 223412 at 1 and 10 µM (EC50 = 270.8 ± 78.9 µM and 388.3 ± 105.5 µM, respectively). Although the authors demonstrated that SB 223412, [MePhe7]-NKB, and senktide are potent and selective for the tachykinin NK3 receptors in binding and functional (Ca(2+) mobilization) assays, the tachykinin NK1-receptor antagonist CP 99,994 at 1 µM (EC50 = 32.7 ± 8.5 µM) produced inhibition of [MePhe7]-NKB-induced bronchoconstriction, whereas the tachykinin NK2-receptor antagonist SR 48968 at 0.1 µM (EC50 = 213.2 ± 42.9 µM) blocked senktide-induced bronchoconstriction. These data suggest that [MePhe7]-NKB and senktide caused bronchoconstriction in guinea pig through activation of the tachykinin NK3-receptors but the tachykinin NK1- and/or NK2-receptors are also involved in the response.
Subject(s)
Bronchoconstriction/drug effects , Bronchoconstrictor Agents/pharmacology , Lung/drug effects , Peptide Fragments/pharmacology , Quinolines/pharmacology , Receptors, Neurokinin-3 , Substance P/analogs & derivatives , Animals , CHO Cells , Cricetinae , Cricetulus , Disease Models, Animal , Guinea Pigs , In Vitro Techniques , Lung/physiology , Male , Piperidines/pharmacology , Receptors, Neurokinin-3/antagonists & inhibitors , Receptors, Neurokinin-3/biosynthesis , Substance P/pharmacologyABSTRACT
BACKGROUND: Functional alpha1- and alpha2-adrenoreceptor subtype pharmacology was characterized in an in vitro human nasal mucosa contractile bioassay. METHODS: Nasal mucosa was obtained from 49 donor patients and mucosal strips were placed in chambers filled with Krebs-Ringer solution and attached to isometric force transducers. RESULTS: Nonselective a-adrenoreceptor agonists epinephrine, norepinephrine, and oxymetazoline produced concentration-dependent contractions of isolated human nasal mucosa (pD2 = 5.2, 4.9, and 6.5, respectively). The alpha2-adrenoreceptor agonist BHT-920 (10 microM)-induced contractions were blocked by yohimbine (0.01-1 microM) and prazosin (0.01-1 microM) inhibited the contractile response to the alpha1-adrenoreceptor agonist phenylephrine (10 microM). Histological analysis showed that phenylephrine and BHT-920 differentially contracted the arteries and veins of human nasal mucosa, respectively. CONCLUSION: Our results indicate that functional alpha1- and alpha2-adrenoceptors are present and functional in human nasal mucosa. The alpha2-adrenoceptors display a predominant role in contracting the veins and the alpha1-adrenoceptors appear to preferentially constrict the human nasal arteries.
