A fraction resembling oxytocin from Squalus acanthias: Pharmacological comparisons with synthetic peptides

Sawyer, Wilbur H.; Baxter, J. W. M.; Manning, Maurice; Heinicke, E.; Perks, A. M.

doi:10.1016/0016-6480(70)90096-1

Cited by 6 publications

(2 citation statements)

References 20 publications

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“…This is consistent with the observation that the intact oxytocin ring (containing 3-isoleucine and 4-glutamine) is important in endowing a peptide with high frog bladder activity (Sawyer, Baxter, Manning, Heinicke & Perks, 1970).…”

Section: Resultssupporting

confidence: 85%

4-Threonine Analogues of Neurohypophysial Hormones With Selectively Enhanced Oxytocin-Like Activities

Sawyer¹,

Manning²

1971

Journal of Endocrinology

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The 4-threonine analogues of oxytocin and of mesotocin and isotocin were prepared by solid-phase synthesis. -oxytocin is about twice as active as oxytocin in rat uterus assays in vitro and in vivo and about three times as active in fowl vasodepressor assays. It is slightly more active than oxytocin in rat or rabbit milk-ejection assays. When infused intravenously into water-loaded rats it causes much less depression of diuresis than does an equal dose of oxytocin. [4-Threonine]-oxytocin has much less vasopressor activity than oxytocin. [4-Threonine]-mesotocin also shows enhanced oxytocin-like properties. Its oxytocic activity is equal to or greater than that of oxytocin and its fowl vasodepressor potency is about the same as that of [4-threonine]-oxytocin, 1500 u./mg. It also has less antidiuretic and vasopressor activities than mesotocin. Thus 4-threonine analogues, containing nothing but common L-amino acids, appear to have more of the specific oxytocin-like properties and less of the vasopressin\x=req-\ like properties than do oxytocin or mesotocin. Thus they may be considered improvements on the natural hormones. In this respect they are unique among the reported synthetic analogues of natural peptide hormones.Substitution of 4-threonine in the weakly-active analogue [3-leucine]\x=req-\ oxytocin also increases its oxytocic and fowl vasodepressor activities. Thus a threonine in the 4-position appears to endow oxytocin-like peptides with greater specific activities than do the amino acids that occur naturally in this position, glutamine and serine. These observations may be of interest when considered (a) from an evolutionary viewpoint, (b) in attempting to interpret relations between molecular structures and biological activities, and (c) as describing peptides with more of the desired properties of oxytocin and less of the undesired properties which might have therapeutic advantages over the natural hormone.

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Section: Resultssupporting

confidence: 85%

4-Threonine Analogues of Neurohypophysial Hormones With Selectively Enhanced Oxytocin-Like Activities

Sawyer¹,

Manning²

1971

Journal of Endocrinology

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“…Oxytocin (5), lysine-vasopressin (6) arginine-vasopressin (7), crystalline [1-3-mercaptopropionic acid]-oxytocin (deamino-oxytocin) (8), oxytocinoic acid (9), [4-proline]oxytocin (10), [8-phenylalaninel-oxytocin (11) and [8-serine]-oxytocin (12) were prepared by the solid-phase method of peptide synthesis (13). -oxytocin (14), [7-glycine]-oxytocin (15), [8-alaninel-oxytocin (16), [9-sarcosinamide]-oxytocin (17) and crystalline deamino-dicarbaoxytocin (an oxytocin analog in which the N-terminal amino group is replaced by a hydrogen atom and the disulfide bridge by an ethylene moiety, ref.…”

Section: Methodsmentioning

confidence: 99%

Regulation of Formation and Proposed Structure of the Factor Inhibiting the Release of Melanocyte-Stimulating Hormone

Celis

Taleisnik

Walter

1971

Proc. Natl. Acad. Sci. U.S.A.

167

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Microsomal preparations from the stalk median eminence of female rats are shown to contain an enzymic activity that is responsible for the formation of MSH-release-inhibiting factor (MSH-R-IF). The amount of this activity remains constant throughout the estrous cycle. The corresponding mitochondrial preparations from the stalk median eminence contain another enzymic principle, estrous cycle-dependent, which competes with the enzyme present in the microsomal preparation for the same "substrate", and can thereby prevent the formation of MSH-R-IF.Several neurohypophyseal hormones, analogs, and peptide intermediates have been tested for their intrinsic MSH-R-IF activity and for their ability to be transformed into MSH-R-IF by incubation with microsomal preparations of stalk median eminence from male rats; it is concluded that the enzyme responsible for the formation of MSH-R-IF is an exopeptidase and that the release-inhibiting factor itself is a tripeptide. Oxytocin is converted by the incubation to L-prolyl-L-leucylglycinamide; nanogram amounts of this tripeptide inhibit the release of MSH from the pituitary both in vivo and in vitro.Rat hypothalamus contains a factor (MSH-R-IF) that inhibits the release of melanocyte-stimulating hormone (1, 2). Evidence for the enzymic formation of this factor has been presented (3). In male rats the pituitary content of MSH remains constant, whereas in females it fluctuates as a function of the estrous cycle (4).This last-mentioned finding was the point of departure for investigating the manner in which pituitary MSH content reflects a change in the enzymic activities responsible for the control of MSH-R-IF formation. We show that a microsomal exopeptidase in the hypothalamus degrades oxytocin, liberating the hormonal C-terminal tripeptide, prolyl-leucylThis work has been performed in C6rdoba and New York. Therefore, different strains of rats and of toads (Bufo arenarum, Bufo marinus) were employed. Since the results obtained in the two laboratories showed no discrepancies, combined publication was agreed upon.Abbreviations of amino-acid derivatives and peptides are in accordance with the IUPAC-IUB Tentative Rules on Biochemical Nomenclature, Biochemistry, 5, 2485Biochemistry, 5, , 1445Biochemistry, 5, (1966 6, 362 (1967

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Neurohypophysial hormones as molecular evolutionary tracers: investigations on the sturgeons Acipenser stellatus and Acipenser guldenstadti

Rouillé

Chauvet

et al. 1991

Comparative Biochemistry and Physiology Part B: Comparative Bio

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A fraction resembling oxytocin from Squalus acanthias: Pharmacological comparisons with synthetic peptides

Cited by 6 publications

References 20 publications

4-Threonine Analogues of Neurohypophysial Hormones With Selectively Enhanced Oxytocin-Like Activities

4-Threonine Analogues of Neurohypophysial Hormones With Selectively Enhanced Oxytocin-Like Activities

Regulation of Formation and Proposed Structure of the Factor Inhibiting the Release of Melanocyte-Stimulating Hormone

Neurohypophysial hormones as molecular evolutionary tracers: investigations on the sturgeons Acipenser stellatus and Acipenser guldenstadti

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