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The isolation of an untriakontapeptide from camel pituitary extracts has been described. Its structure has been determined and shown to be identical to the sequence of carboxyl-terminal 31 amino acids of ovine f-lipotropin.The peptide possesses very low lipotropic activity but significant opiate activity.During the course of isolation of melanotropins from camel pituitary glands (1), we obtained an untriakontapeptide that has an amino-acid sequence identical to the COOH-terminal 31 residues of ovine fl-lipotropin (2-4). This peptide was found to possess opiate activity. This article describes the isolation, amino-acid sequence, and biological activity of the untriakontapeptide. EXPERIMENTALThe starting material was component N, which was obtained by chromatography of fraction D on a carboxymethyl-cellulose column (1). Fraction D was prepared from acid acetone extracts of whole camel (Camelus dromedarius) pituitaries. Component N was purified further by gel filtration on Sephadex G-25 (fine), followed by electrophoresis on Whatman no. 3 MM paper in pyridine-HOAc buffer, pH 3.7 (pyridine-HOAc-H20, 4:40:1150 vol/vol) for 2 hr at 400 V.Trypsin was obtained from Calbiochem and subtilisin from Sigma. Digestions were performed with 1 mg of peptide and 0.02 mg of trypsin or 0.05 mg of subtilisin in 0.2 M NH4OAc, pH 8.0, at 370 for 8 hr for trypsin and 1 hr for subtilisin. The digests were mapped by paper chromatography (butanol-HOAc-H20, 4:1:5 vol/vol) and subsequent high voltage electrophoresis at pH 2.0 [HCOOH (88%)-HOAc-H20, 218:63:719 vol/vol] for 1.5 hr at 2000 V. Maps were sprayed with 1% ninhydrin in ethanol solution and allowed to develop in the dark for 20 hr; the spots were cut out and material was eluted with 0

The isolation and characterization of a new biologically active polypeptide from sheep pituitary glands is described. Considerable evidence suggests that the structure of the new molecule, designated γ-lipotropin, is identical with the N-terminal portion (sequence 1–58) of β-lipotropin and, therefore, that γ-lipotropin contains at its C-terminus the amino acid sequence of β-melanophore-stirnulating hormone (β-MSH). The implications of these results are discussed in relation to the mechanism of pituitary peptide biosynthesis and to the structure–activity relationships between sheep β-MSH and lipotropic hormones.

The pharmacokinetics and the hormonal, analgesic, and behavioral effects of several doses of human a-endorphin were evaluated after intravenous administration to three patients and intracerebroventricular administration to one patient with pain caused by cancer. These effects were compared to the hormonal effects of intravenously administered morphine sulfate in two patients and an enkephalin analog in two baboons. The mean terminal half-life after intravenous administration of 5 or 10 mg of human f-endorphin to three patients was 37 min; the mean volume of distribution was 178 ml/kg, and the metabolic clearance rate was 3.2 (ml/min)/kg.The half-life of P-endorphin in cerebrospinal fluid after intracerebroventricular administration was 93 min, and the volume of distribution was 0.74 ml/kg. A rapid rise in plasma prolactin followed both intravenous and intracerebroventricular a-endorphin. Intravenous administration did not affect plasma growth hormone, but intracerebroventricular administration suppressed plasma growth hormone. No significant change in plasma growth hormone was noted after intravenous administration of morphine to humans, but plasma growth hormone decreased in one baboon after administration of the enkephalin analog. P-Endorphin-stimulated release of prolactin occurred at doses lower than those required to produce analgesic and other behavioral effects. When both hormonal and analgesic effects were observed (after 7.5 mg were given intracerebroventricularly), the onset of the hormonal response slightly preceded the analgesic and behavioral responses. These studies suggest that the hormonal effects of ,-endorphin are species dependent and are similar to those of morphine. Hormonal and analgesic effects of ,-endorphin appear to result from the activation of opiate receptors that differ in their locations and characteristics.Intracerebroventricular (icv) administration of f3-endorphin causes similar physiological and pharmacological effects in several animal species (1, 2). In contrast, intravenous (iv) administration of ,B-endorphin causes different effects in different species. In the rat there is no demonstrable behavioral effect after iv doses of f3-endorphin up to 30 mg/kg (3), whereas in the cat doses as low as 50-500 jug/kg produce behavioral changes (4). Preliminary studies in humans (5-7), using a wide dose range of human fl-endorphin (f.h-ep), revealed both behavioral and analgesic effects. In the present study, we have assessed the pharmacologic disposition, as well as the concurrent hormonal, analgesic, and behavioral effects of Oh-ep administered in various doses iv to three cancer patients with pain and icv to one other cancer patient with pain. We administered an enkephalin analog, [2-D-alanine,5-norleucinelenkephalinamide, to two baboons to evaluate whether the hormonal and behavioral effects of opioid peptides were similar in nonhuman primates without pain or previous exposure to opiate drugs. 100 ,ug to 7.5 mg at 1-2 week intervals over a 10-week period; the reservoir had...