Previous studies of noradrenergic mechanisms in spontaneously hypertensive rats (SHR) have yielded conflicting results, as many have used: 1) rats of only one age; 2) a single organ such as heart or brain; or 3) either Wistar-Kyoto (WKY) or an outbred normotensive control rat. We have studied the turnover of norepinephrine (NE) in three brain areas (cortex, hypothalamus, brain stem) and three p...

A shift of pH of pepsin solutions from 4.6 to 1.0 gives rise to spectral displacemerits in the ultraviolet. If represented as difference spectra three peaks with maxima at 2770, 2850, and 2930 ,~mgstr~ms are present which can be attributed to the tyrosine and tryptophan residues in the protein. On mild autolysis of pepsin at pH 2.0 the absorbancy in the ultraviolet further decreases. Although s...

The present investigation was undertaken to see if any of the naturally occurring vasoactive substances was likely to act as a mediator for the pulmonary vasoconstrictor response to acute alveolar hypoxia. Rats were treated with agents that deplete local stores of vasoactive amines or inhibit their synthesis. Lungs from these animals were isolated, ventilated, and perfused with homologous blood...

Two types of conditioned behaviors were investigated for the purpose of evaluating anxiolytic drugs. A conditioning procedure used was an active avoidance in poorly-performing mice. Chlordiazepoxide, diazepam, chlorazepate and meprobamate increased the avoidance rate, while chlorpromazine, haloperidol and nortriptyline did not produce such an effect. The effect of diazepam was potentiated by ga...

The effects of peripheral administration of 6-(R)-5,6,7,8-tetrahydro-L-erythrobiopterin dihydrochloride (R-THBP), a natural cofactor for tyrosine and tryptophan hydroxylases, were investigated in mice treated with a competitive inhibitor of tyrosine hydroxylase, alpha-methyltyrosine (alpha-MT). A subcutaneous dose of 250 mg/kg of alpha-MT decreased markedly both ambulatory activity and cerebral...

We describe an automated procedure for protein design, implemented in a flexible software package, called Proteus. System setup and calculation of an energy matrix are done with the XPLOR modeling program and its sophisticated command language, supporting several force fields and solvent models. A second program provides algorithms to search sequence space. It allows a decomposition of the syst...

Two classes of compounds have been investigated as inhibitors of purified beef adrenal tyrosine hydroxylase. Among the aromatic amino acids tyrosine analogues were found to be most potent, particularly those having an a-methyl or 3-halogen substitution. Two normal metabolites, monoand diiodo-tyrosine, were found to bevery effective inhibitors. Inhibition by the amino acid analogues was shown to...

Cholinergic Properties of the Relay Junctions of the Primary Afferent Pathway. D. T. FRAZIER AND L. L. BOYARSKY 1 Monoamine Levels and Neuronal Degeneration in Rat Brain following Lateral Hypothalamic Lesions. ROBERT Y. Moons AND ALFRED HELLER 12 Localization of Tritiated Serotonin in Rat Brain by Electron-Microscopic Autoradiography. GEORGE K. AGHAJANIAN AND FLOYD E. BLOOM 23 The Effect of Dru...

Antagonists of human growth hormone-releasing hormone (hGHRH) with increased potency and improved enzymatic and chemical stability are needed for potential clinical applications. We synthesized 21 antagonistic analogs of hGHRH(1–29)NH2, substituted at positions 8, 9, and 10 of the common core sequence {phenylacetyl-Tyr1, D-Arg2,28, para-chloro-phenylalanine 6, Arg9 homoarginine 9, Tyr10 O-methy...

The ability to genetically incorporate unnatural amino acids (UAAs) at specific sites in the proteome of living cells provides a powerful tool to both investigate and engineer protein structure and function. A reassigned nonsense or frameshift codon is used to encode the UAA of interest, and an orthogonal aminoacyl-tRNA synthetase/tRNA (aaRS/ tRNA) pair specific for the UAA delivers the latter ...