Oxytocin protein bindings

Similarly, though plasma protein binding data were not ostensibly used in the identification of an oxytocin antagonist suitable for advancement to the clinic, such data were used to explain the differences between in vivo and in vitro potency [46]. 

Antidiuretic hormone (ADH) and oxytocin are synthesized in the supraoptic and paraventricular nuclei in the brain and are transported in secretory granules through axons to the posterior lobe. These hormones are cyclic peptides of eight amino acids. Each is synthesized as a larger precursor, which is processed into the hormone plus a protein that binds the hormone, called neuro-physin. ADH and oxytocin have different amino acids at positions 3 and 8. 

Neurophysin A protein that is secreted with oxytocin and vasopressin from the posterior pituitary gland. Neurophysin binds to these two hormones and stabihzes them. 

Sirotkin, A.V., Makarevich, A.V., M.R. Corkins, Kotwica, J., Kwon, H.B., Bulla, J., and Hetenyi, L. (2001) Secretory Activity of Bovine Ovarian Granulosa Cells Transfected with Sense and Antisense Insulin-Like Growth Factor (IGF) Binding Protein-3 and the Response to IGF-I, GH, LH, Oxytocin and Estradiol, J. Mol. Endocrinol. 27, 329-338. 

The analogs discussed so far reveal certain features of the various oxytocin receptors. The molecule binds, however, not merely to the receptors in the target organs, but also to a carrier protein, originally known as the van Dyke protein [54] that was renamed neurophysin after its isolation in pure form. It is rather remarkable that for binding of oxytocin to this protein the free N-terminal amino group, which is not needed for activity, is quite essential [55]. 

Neurophysins small proteins associated with the hormones oxytocin and vasopressin. In bovines, oxytocin-like arginine vasopressin and N.n are synthesized from a single polypeptide precursor, as are oxytocin and N. I. Most species have more than two N., but usually there are two major N.The middle sequence of N. is conserved, and the N. differ in their terminal sequences. The N. bind to the neurohormones with which they are synthesized and are secreted with them into the blood. The biological function, if any, of the N. is not known. [H. Land et al. Nature 302 (1983) 342-344 A. G. Robinson in D.T. Krieger J.C Hughes (eds.) Neuroendocrinology (Sinauer Assoc., Sunderland, Mass., 1980)]... 

The active polypeptides in the secretory granules are probably not present in a free form. Van Dyke has isolated a protein called neurofisin (mol wt 30,000), which apparently binds 1 molecule of vasopressin and 1 molecule of oxytocin. The nature of the bond between the active hormone and the supporting protein is unknown. 

The complexes formed by neurophysin-M contained 3 Moles of vasopressin, or 2 Moles of oxytocin or 2 Moles of vasopressin and 1 Mole of oxytocin per Mole of protein It appears that oxytocin competes with vasopressin for one of the binding sites. Neurophysin-II, a constituent of neurophysin-M, forms crystalline complexes containing 2 Moles of vasopressin or 2 Moles of... 

The binding of two Moles of oxytocin by neurophysin-II and neurophysin-M is in agreement with the finding of Breslow and Abrash for a fraction (E) of bovine neurophysin. The native neurophysin-I has been found to bind three Moles of oxytocin per Mole of protein. Neurophysin-I would have been absent from the preparations of neurophysin used by Breslow and Abrash 52 ... 

II and -M. The number of moles of vasopressin bound per mole of any one of the three proteins was reduced in the presence of oxytocin. This is almost certainly because of a competition for certain peptide binding sites by oxytocin. It is interesting to note that the non-mammalian hormone 8-arginine vasotocin is bound by mammalian neurophysin In addition, Breslow... 

Formation of the oxytocin-neurophysin complex results in unob-servably broad resonances. Slow exchange does not occur because in this case two states should be observed, the bound (with a very broad resonance) and the free (with a narrow resonance). The N-terminal tripeptide does not bind to neurophysin, and its spectrum was unaffected by the presence of neurophysin. The line broadening of the deuterium label can be a sensitive monitor of hormone-protein interaction. However, in many cases only qualitative information will be obtainable, i.e., when the breadth of the lines renders them practically unmeasurable. Few other direct studies on peptides using quadrupolar nuclei have been reported, but with increasing instrumental sophistication it can be anticipated that greater use of these nuclei will be made in the future. 

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