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.

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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.

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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.

SUMMARY1. The effects of changes of ionic environment upon corticosteroid production by rabbit adrenal glands have been investigated in vitro using a superfusion technique and on-line steroid analysis by an automated fluorescence method. In some experiments micro-electrode recordings of adrenocortical transmembrane potentials were made concomitantly with measurement of steroid output.2. Adrenocorticotrophic hormone (ACTH), 10 m-u./ml., induced a sevenfold increase in corticosteroid production rate in normal Krebs solution.3. The steroidogenic response to ACTH was not impaired after omission of [K]. for 1 hr but was inhibited following exposure to K+-free medium for 3 hr. Increase of [K]. tenfold to 47 mm increased the basal but not the ACTH-stimulated output of corticosteroid whereas raising [K]o twentyfold to 94 mm enhanced both the basal and ACTH-stimulated steroid production rate. In K+-free solution the adrenocortical cells hyperpolarized from -67 to -86 mV; subsequently on addition of ACTH they depolarized. Reintroduction of K+ restored the membrane potential. 6. Nupercaine, 104 M, inhibited the steroid response to ACTH with no effect upon membrane potentials: increasing the nupercaine concentration to 10-3 M inhibited the steroid response and depolarized the cells. Ouabain, 10-5 M, induced complete depolarization and suppression of the steroidogenic response to ACTH.7. Action-potential-like changes in membrane potential appeared in cells exposed to ACTH in a K+-free medium. The amplitude of the action potentials ranged from 10 to 60 mV according to cell, with a frequency up to 36/min; the frequency tended to increase with time. Tetrodotoxin, 1046g/ml., did not inhibit ACTH-induced action potentials in K+-free medium.8. These observations are discussed in relation to the ionic requirements for the steroidogenic action of ACTH. The results further emphasize the dissociation of membrane polarization and the secretion of steroid. The mechanism of output of steroid hormone from the adrenocortical cell may thus differ fundamentally from the secretary mechanisms in other, particlestoring cells.

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