Oxytocin hormonal activity

More complex polypeptides, many of which also exhibit hormonal activity, have been implicated in the functioning of the CNS. Neurotensin, angiotensin II, oxytocin, vasopressin, somatostatin, thyrotropin- releasing... 

Hormones related to oxytocin and vasopressin occur in most vertebrates, the compound vasotocin shown in Fig. 30-4 being the most common. Substitution of phenylalanine for isoleucine at position 3 gives arginine vasopressin, the vasopressin found in our bodies. Structure of oxytocin and related hormones82 are also shown in Fig. 30-4. Like somatostatin, vasopressin and oxytocin may also form antiparallel pleated sheet structures with P turns. The structural requirements for hormone activity have been studied intensively. Both the macrocyclic hexapeptide ring and the tripeptide side chains are necessary for maximal activity.83... 

The seeds of Vaccaria segetalis (Caryophyllaceae) have been used to stimulate blood flow and promote milk secretion, and also to treat amenorrhea and breast infections in China (224). Extraction and purification of chemical constituents showing follicle hormonic activity led to the isolation of the new, bioactive cyclic peptides segetalins A-H (322-329) (225-228). Some segetalins showed potent estrogen-like activity. Although some cyclic peptides such as oxytocin and vasopressin show hormone activities, none show estrogen-like activity. 

Clark D (2004) Characteristics of nearly dry enzymes in organic solvents implications for biocatalysis in the absence of water. Philos Trans R Soo London B 359 1299-1307 Du Vigneaud V, Ressler C, Swan J et al. (1953) The synthesis of an octapeptide amide with the hormonal activity of oxytocin. J Am Chem Soc 75 4879 880 Ellman GL (1958) A colorimetric method for determining low concentrations of mercaptans. Arch Biochem Biophys 74 443-450... 

Dimerization of the oxytocin molecule by incubation in NaHC03 at pH 8.3 at room temperature yields a biologically inactive compound. When vasopressin is incubated with cysteine or glutathione, the reduction of the disulfide bridge diminishes antidiuretic activity to one-third of its original value. The substitution of the 8-lysine of vasopressin by 1-deamino lysine enhances the antidiuretic activity, but substitution of the 8-lysine by 1-acetyllysine abolishes most of the hormonal activity. 

We successfully used electro-deprotection reactions in the synthesis of various classes of natural compounds, such as amino acids, oligopeptides, glycoproteins, phospholipids, saccharides, polysaccharides, etc. [279-283]. Application of the method instead of chemical synthesis of oxytocin and desamino-oxytocins led, for example, to a twofold increase in the yield of these hormones with high degree of hormonal activity (joint work with the Riga s chemists [284]). 

N-terminal amino-group. Suppression of the N-terminal amino-group enhances oxytocin-like activities and antidiuretic activities but decreases pressor activities. The antidiuretic activity of de-amino -arginine-vasopressin is 3 times higher than the natural hormone. 

Oxytocin and Vasopressin Receptors. The actions of oxytocin and vasopressin are mediated through their interactions with receptors. Different receptor types as well as different second messenger responses help explain their diverse activities in spite of the hormones stmctural similarities. Thus oxytocin has at least one separate receptor and vasopressin has been shown to have two principal receptor types, and V2. Subclasses of these receptors have been demonstrated, and species differences further compHcate experimental analysis. It is apparent that both oxytocin and receptors function through the GP/1 phosphoHpase C complex (75), while the V2 receptors activate cycHc AMP (76). 

Several human receptors for the neurohypophyseal hormones have been cloned and the sequences elucidated. The human V2 receptor for antidiuretic hormone presumably contains 371 amino acids and seven transmembrane segments and activates cycHc AMP (76). The oxytocin receptor is a classic G-protein-coupled type of receptor with a proposed membrane topography also involving seven transmembrane components (84). A schematic representation of the oxytocin receptor stmcture within the membrane is shown in Eigure 4 (85). 

Many hormones and other blood-borne substances (including drugs) also alter contractile activity of smooth muscle. Some of the more important substances include epinephrine norepinephrine angiotensin II vasopressin oxytocin and histamine. Locally produced substances that may alter contraction in the tissue in which they are synthesized include nitric oxide prostaglandins leukotrienes carbon dioxide and hydrogen ion. 

Progesterone produces direct membrane effects [16]. These include actions that promote maturation of spermatozoa as well as oocytes and facilitation of the release of neurotransmitters such as dopamine and LH-releasing hormone (LHRH) (Fig. 52-7). Membrane actions of progesterone also activate oxytocin receptors in the hypothalamus in a way that enables oxytocin to turn on sexual behavior in the estrogen-primed female rat [3],... 

None of these findings undermines the importance of the intracellular genomic actions of steroids. Rather, they increase the richness of the cellular actions of steroid hormones and raise the possibility that there may be connections between genomic and nongenomic actions of steroids. For example, genomic action may induce receptors that mediate nongenomic effects. Moreover, the activation of oxytocin receptors by progesterone is dependent... 

Because neuropeptides are active in very small amounts within the CNS they are more difficult to manipulate and study than steroid hormones. In addition, at present there is no simple method for administering neuropeptides within the CNS. (In animals, it is necessary to inject chemicals or their antagonists directly into the CNS, which is not feasible in humans.) Thus, most research on the behavioral effects of either oxytocin or vasopressin in humans is correlational, and subsequently difficult to interpret. However, animal studies also support the hypotheses described here (Carter, 1992 Uvnas-Moberg, 1996). 

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