The oral administration of peptide drugs is well known to be precluded by their digestion in the stomach and small intestine. As a new approach to oral delivery, peptide drugs were coated with polymers cross-linked with azoaromatic groups to form an impervious film to protect orally administered drugs from digestion in the stomach and small intestine. When the azopolymer-coated drug reached the large intestine, the indigenous microflora reduced the azo bonds, broke the cross-links, and degraded the polymer film, thereby releasing the drug into the lumen of the colon for local action or for absorption. The ability of the azopolymer coating to protect and deliver orally administered peptide drugs was demonstrated in rats with the peptide hormones vasopressin and insulin.
The release of AC'I'H by rat anterior pituitary tissue i n vitro was usetl ;I.., a test system for the detection of factors that sti~nulate ,4C'TH-release. 'I'he results indicate that:1. Epinephrine or arterenol, added by themselves, are without eifect. 2. Hypothalan~ic tissue alone is also ineflective. 3. 'The combination of hypothalamic tissue with epinephrine or arterenol increases the release of AC'I'H about threefold.4. Brain cortex can replace hypothalanlus. 5. Liver cannot replace neural tissue; acetyl choline ant1 serotonin cannot replace epinephrine or arterenol.6. The greatest stimulation of ACTH-release (six-to eight-fold) occurs with posterior pituitary tissue plus arterenol. The arterenol rnay be replaced by hypothalamus or sphingosine, but not by dopamine (3,4-dihydrox~.phei1~.leth~-lamine), which is structurally similar to arterenol.7. The posterior pituitary is probably involved in the response of the anterior pituitary-adrenocortical systern to stress.
The release of ACTH by rat anterior pituitary tissue in vitro was used as a test system for the detection of factors that stimulate ACTH-release. The results indicate that:1. Epinephrine or arterenol, added by themselves, are without effect.2. Hypothalamic tissue alone is also ineffective.3. The combination of hypothalamic tissue with epinephrine or arterenol increases the release of ACTH about threefold.4. Brain cortex can replace hypothalamus.5. Liver cannot replace neural tissue; acetyl choline and serotonin cannot replace epinephrine or arterenol.6. The greatest stimulation of ACTH-release (six- to eight-fold) occurs with posterior pituitary tissue plus arterenol. The arterenol may be replaced by hypothalamus or sphingosine, but not by dopamine (3,4-dihydroxyphenylethylamine), which is structurally similar to arterenol.7. The posterior pituitary is probably involved in the response of the anterior pituitary–adrenocortical system to stress.
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