The Action of Oxytocin and Synthetic Analogues on the Isolated Mammary-Gland Myoepithelium of the Lactating Rat; Effect of Some Ions

Poláček, Ivo; Krejcí, I; Rudinger, J.

doi:10.1677/joe.0.0380013

Cited by 17 publications

(4 citation statements)

References 18 publications

(31 reference statements)

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“…Moore et al [15] reported that myoepithelial cells in the tissue of mammary glands failed to contract in the presence of oxytocin after a 30-min incubation in a Ca 2+ -free solution at 37°C. Polácek et al [20] reported that mammary tissue strips contracted in response to oxytocin in a Ca 2+free solution, but that the response gradually decreased and disappeared upon further incubation in the same solution. In our study, oxytocin induced the contraction even 30 min after perfusion in the Ca 2+ -free solution, although the amplitude of the Ca i 2+ increase was reduced.…”

Section: Discussionmentioning

confidence: 99%

Involvement of P 2 -purinergic receptors in intracellular Ca 2+ responses and the contraction of mammary myoepithelial cells

Nakano

Furuya

et al. 1997

Pfl�gers Archiv European Journal of Physiology

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Mammary myoepithelial cells were isolated and cultured to characterize their properties. The intracellular calcium concentration (Cai2+) was measured using the ratio of fura-2 fluorescence at 340 nm to that at 360 nm (F340/F360), and the contraction was simultaneously monitored by the change of fluorescence intensity at 360 nm (F360). Cultured myoepithelial cells retained their contractile machinery as in the intact tissue. NBD-phallacidin fluorescence, which marks F-actin, and electron microscopy showed abundant bundles of microfilaments in the cytoplasm. Oxytocin (> 0.1 nM) induced an increase in Cai2+ and contraction. The amplitude and time course of the Cai2+ increase were not markedly affected in the Ca2+-free solution. Nifedipine (10 microM) did not affect the response to oxytocin. ATP (>1 microM) induced an increase in Cai2+ and contraction. The response to ATP was not affected by Ca2+ removal, but was suppressed by suramin (100 microM), an antagonist of P2-purinergic receptors. The order of potency of nucleotides to increase Cai2+ was ATP = ADP > UTP > UDP. These findings indicate the presence of P2-purinergic receptors in mammary myoepithelial cells. The results suggest that stimulant-induced Cai2+ increases and contractions are due to release of Ca2+ from intracellular stores in these cells. In addition to the hormonal action of oxytocin, extracellular nucleotides may function as paracrine agents to contract myoepithelial cells in the mammary gland.

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Section: Discussionmentioning

confidence: 99%

Involvement of P 2 -purinergic receptors in intracellular Ca 2+ responses and the contraction of mammary myoepithelial cells

Nakano

Furuya

et al. 1997

Pfl�gers Archiv European Journal of Physiology

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“…Both protected intermediates and that of [Gly7]oxytocin4 were converted to the disulfide-bridged cyclic peptides and the products purified by methods described previously.10,14 '15 The pharmacological properties of [Gly7]oxytocin, [Thr4,Gly7]oxytocin, and hydroxy[Thr4,Gly7]oxytocin were evaluated by methods previously described16™18 and by assays on isolated strips of rat mammary gland. 19…”

mentioning

confidence: 99%

Synthesis and some pharmacological properties of [4-threonine,7-glycine]oxytocin, [1-(L-2-hydroxy-3-mercaptopropanoic acid),4-threonine,7-glycine]oxytocin (hydroxy[thr4, gly7]oxytocin), and [7-glycine]oxytocin, peptides with high oxytocic-antidiuretic selectivity

Lowbridge¹,

Manning²,

Haldar³

et al. 1977

J. Med. Chem.

102

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[4-Threonine, 7-glycine]oxytocin and [1-(L-2-hydroxy-3-mercaptopropanoic acid), 4-threonine, 7-glycine]oxytocin (hydroxy[Thr4, Gly7]oxytocin) were synthesized by a combination of solid-phase and classical methods of peptide synthesis. A protected octapeptide was synthesized by the solid-phase method and following ammonolysis and purification 1 + 8 couplings in solution were employed to furnish the required key nonapeptide and acyl octapeptide intermediates, respectively. [7-Glycine]oxytocin was prepared from a sample of the protected nonapeptide intermediate used in the original synthesis of this peptide. [7-Glycine]oxytocin has an oxytocic potency (O) of 93 +/- 4 units/mg and an antidiuretic potency (A) of 0.0056 +/- 0.0003 units/mg. It has an O/A ratio of 16 000. [4-Threonine, 7-glycine]oxytocin has an oxytocic potency of 166 +/- 4 units/mg and an antidiuretic potency of 0.002 +/- 0.0004 units/mg. Its O/A ratio is 83 000. Threonine substitution has thus brought about a substantial enhancement in oxytocic activity and a fivefold enhancement in O/A selectivity. Hydroxy [Thr4, Gly7]oxytocin has an oxytocic potency of 218 +/- 8 units/mg and antidiuretic potency of 0.0040 +/- 0.0005 units/mg. Its O/A ratio is thus 54 500. All three 7-glycine-substituted analogues exhibit a marked sensitivity to Mg2+ on the rat uterus assay ststem and in the presence of 0.5 mM Mg2+ had oxytocic potencies in the range of 900-1000 units/mg. Should these peptides exhibit enhanced oxytocic selectivity in humans, they might offer a greater margin of safety than oxytocin in those clinical stiuations in which the latter is currently employed.

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“…In the lactating guinea-pig (Bisset, 1964) methyloxytocin, like oxytocin, increases milk-ejection pressure. It also contracts the mammary gland strip in vitro, but the rate of contraction is slower than with oxytocin and the onset of tachyphylaxis is more rapid; with ethyloxytocin these anomalies become more pronounced (Polacek et al, 1967). On the mammary gland, carbamoyl-methyloxytocin, though it invariably inhibits the response to oxytocin, does retain some remnants of oxytocin-like activity.…”

Section: Discussionmentioning

confidence: 99%

“…A strip 3 cm x 0 5 cm x 0 5 cm was suspended in a 10 or 12-5 ml organ bath at 380 C containing Tyrode's solution: (mM) NaCl 137, KC1 217, NaHCO3 11 9, NaH2PO 0-42, CaCl2 0 9-1P8, MgCl2 0-1'0, glucose 5-6, gassed with a mixture of 95% oxygen and 5% carbon dioxide. Before use, the strip was stored overnight in Tyrode's solution at 40 C. Tension was recorded isometrically by the same method as that used for the isolated uterus or with a Briiel-Kjaer strain-gauge and recorder (Polacek, Krejci & Rudinger, 1967). An initial tension of 400-500 mg was applied and the tissue allowed to equilibrate for 1-2 h before use.…”

mentioning

confidence: 99%

Some pharmacological properties of a synthetic oxytocin analogue [1‐N‐carbamoyl‐hemicystine‐2‐O‐methyltyrosine]‐oxytocin (carbamoyl‐methyloxytocin), an antagonist to the neurohypophysial hormones

Bisset

Clark

Krejcí

et al. 1970

British J Pharmacology

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An antagonist to neurohypophvsial hormones quiescent uterus by the intravenous infusion of oxytocin was interrupted by intravenous injections of the analogue. 5. The response of the isolated strip of rat mammary gland to the analogue depended on whether or not magnesium was present in the bath solution. In the presence oe.this ion, the analogue generally caused an increase in tension; in its absence, it acted as a pure antagonist. As on the isolated uterus, oxytocin and vasopressin were equally inhibited, and the analogue caused a parallel displacement of the log dose-response curve for oxytocin. With 0 9 mm Ca and 1I0 mm Mg, the mean pA2 value (2 min contact) was 6-28 +0-08 (S.E.) 6. In the lactating rat, the analogue inhibited the milk-ejection response to oxytocin and vasopressin but not that to acetylcholine, bradykinin or 5-hydroxytryptamine. A milk-ejection response to the analogue itself was seen occasionally with retrograde arterial but not with intravenous injections. 7. The analogue inhibited the avian depressor response to oxytocin and the rat pressor response to vasopressin. 8. On all assay preparations, the degree of inhibition caused by the analogue was dependent on the dose, and the inhibition could be surmounted by increasing the dose of agonist. Recovery usually occurred within 15 min. These features, together with the parallel displacement of the dose-response curve for oxytocin on the isolated uterus and mammary strip, and the equal inhibition of the responses to oxytocin and vasopressin, suggest that carbamoyl-methyloxytocin acts as a specific competitive inhibitor of the neurohypophysial hormones. 9. The structure-activity relationships of analogues of oxytocin having substituents in the terminal amino and phenolic hydroxyl groups, and some practical applications of the carbamoyl-methyl analogue, are discussed.

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The Action of Oxytocin and Synthetic Analogues on the Isolated Mammary-Gland Myoepithelium of the Lactating Rat; Effect of Some Ions

Cited by 17 publications

References 18 publications

Involvement of P 2 -purinergic receptors in intracellular Ca 2+ responses and the contraction of mammary myoepithelial cells

Involvement of P 2 -purinergic receptors in intracellular Ca 2+ responses and the contraction of mammary myoepithelial cells

Synthesis and some pharmacological properties of [4-threonine,7-glycine]oxytocin, [1-(L-2-hydroxy-3-mercaptopropanoic acid),4-threonine,7-glycine]oxytocin (hydroxy[thr4, gly7]oxytocin), and [7-glycine]oxytocin, peptides with high oxytocic-antidiuretic selectivity

Some pharmacological properties of a synthetic oxytocin analogue [1‐N‐carbamoyl‐hemicystine‐2‐O‐methyltyrosine]‐oxytocin (carbamoyl‐methyloxytocin), an antagonist to the neurohypophysial hormones

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