Effects of stressful procedures as ether anesthesia and intracranial injections on amino acid incorporation into brain protein.

Ether anesthesia elevates plasma corticosterone levels considerably and interferes severely with the incorporation of centrally applied [3 H] leucine into brain protein. Only minor changes in leucine incorporation are observed in conscious rats with an implanted cannula in the third brain ventricle as compared to noncannulated controls. Injection through this cannula can be regarded as a minor stressful procedure comparable to subcutaneous injection both causing moderate elevations in plasma corticosterone levels.

ACTH, cyclic nucleotides, and brain protein phosphorylation in vitro.

Endogenous phosphorylation of proteins from rat brain synaptosomal plasma membranes was studied in vitro. Cyclic AMP (cAMP) markedly stimulated(32)P incorporation in three protein bands with molecular weights of 75,000, 57,000, and 54,000, respectively. The effect of the behaviorally active peptide ACTH1-24 on this endogenous phosphorylation in vitro was studied using peptide concentrations from 10(-10) to 10(-4) M.

Interaction between ACTH fragments, brain opiate receptors and morphine-induced analgesia.

The present study confirms that N-terminal fragments of ACTH have an affinity for rat brain opiate receptors in vitro. Such peptides, devoid of corticotrophic activity, were found to inhibit morphine-induced analgesia if they also possessed affinity for opiate receptors in vitro. The structure-activity relationship for these two parameters is comparable to that observed for the same peptides on the induction of excessive grooming.

Opiate antagonists suppress ACTH(1-24)-induced excessive grooming in the rat.

Intraventricular injection of ACTH(1-24) in rats induces excessive grooming behavior, and subsequent peripheral administration of specific opiate antagonists suppresses this peptide-induced grooming response. Intraventricular injection of morphine mimics both in intact and hypophysectomized rats' - to a certain extent - peptide-induced grooming. The results suggest similarities in the interaction of morphine and ACTH(1-24) with central nervous structures.

Impaired development of tolerance to morphine analgesia in rats with hereditary diabetes insipidus.

Recently it was reported that vasopressin facilitates the development of resistance to the analgestic action of morphine. Therefore, the development of tolerance to daily administration of morphine-HCl (10 mg/kg i.p.

ACTH and brain RNA: changes in content and labelling of RNA in rat brain stem.

The influence of synthetic ACTH1-24 and ACTH1-10 on rat brain RNA was studied. ACTH1-24 (5 IU/100 g s.c.

Incorporation of [3H] leucine into brain stem protein fractions: the effect of a behaviorally active, N-terminal fragment of ACTH in hypophysectomized rats.

In hypophysectomized rats, the incorporation of [3H] leucine into rat brain stem protein, measured 5 min after injection of the precursor into the diencephalon, was decreased. Chronic treatment of these rats with the N-terminal fragment of ACTH, ACTH1-10 increased the incorporation rate. Brain stem proteins were sequentially extracted with a hypotonic buffer, Triton X-100 and SDS.

ACTH-like peptides and opiate receptors in the rat brain: structure-activity studies.

The present study aims at further identifying the interaction of ACTH-like peptides and rat brain opiate receptors in vitro. The sequence ACTH4-10 is crucial with respect to affinity since it is the shortest sequence to inhibit the binding of [3H]-dihydromorphine and [3H]-naltrexone to these receptors. A second active site seems to be localized in the N-terminal part of ACTH11-24.

Influence of peptides on reduced response of rats to electric footshock after acute administration of morphine.

Acute treatment of rats with morphine (10 mg/kg) resulted in a marked reduction of motor response to inescapable electric footshock (EFS). Nalorphine (2mg/kg) antagonized this action of morphine. Pretreatment with synthetic ACTH 1-24 (10 IU) 60 min prior to testing also inhibited this morphine-induced reduction, whereas other ACTH-like peptides, lacking corticotrophic activity, were ineffective.