Vasopressin like

Metal ions such as Cu(II) (566) and Mn(II) (567) react specifically with the hormone vasopressin and vasopressin-like peptides, and this... 

There is particular interest in the nasal mucosa because it can provide systemic absorption of dmgs that otherwise must be administered by injection. These are often polypeptide dmgs. Calcitonin and vasopressin-like dmgs (nonapeptides) for diabetes insipidus in patients with panhypopituitarism are examples. 

Vasopressin likely functions as a CNS neurotransmitter and/or neuromodulator but the physiological relevance of vasopressin s CNS effects is unclear Although vasopressin is not the principal corticotropin-releasing factor it may assist in sustained activation of the hypothalamic-pituitary-adrenal axis during chronic stress (see Chapter 59). CNS effects of vasopressin are mediated predominantly by V receptors. 

Therapeutically, interest in the nasal mucosa for systemic absorption of drugs initially centered on its capability to absorb small to moderately sized polypeptides. For example, vasopressin-like drugs (nonapeptides) may be used to treat diabetes insipidus in patients with panhypopituitarism. This avoids repeated parenteral injections, and avoids the digestive capacity of the gut. 

Thompson, K. S J. and Bacon, J. R (1991) The vasopressin-like immunoreactive (VPLI) neurons of the locust, Locusta migratoria II. Physiology. J, Comp, Physiol 168,619-630. 

The release of NO from the endothelium is induced by various chemical substances, including acetylcholine polypeptides such as substance P, bradykinin, and arginine vasopressin histamine ATP/ADP a2-adrenoceptor agonists thrombin and Ca2+ iono-phores. NO formed in response to mechanical stimuli like shear stress or transmural pressure plays an important role in maintaining basal blood flow. Endothelial NO causes vasodilatation, decreased... 

This peptide itself has no selectivity for the two CCK receptors, CCK-A and B, which have so far been established to stimulate IP3/DAG while, like substance P, can close potassium channels to increase neuronal activity. The CCK-B receptor is thought to predominate in the CNS but species differences may make this interpretation difficult. It has a wide distribution in the CNS but is also found in the gut whereas the CCK-A receptor is more restricted but is found in the hypothalamus, hippocampus and in the brainstem. There are high levels of the natural peptide, CCK-8 in cortex, hippocampus, hypothalamus, ventral tegmentum, substantia nigra, brainstem and spinal cord. CCK is one of the most abundant peptides in the brain and CCK co-exists with dopamine, substance P, 5-HT and vasopressin. Interestingly, in the dopamine areas, CCK co-exists in the mesolimbic pathways but in the nigrostriatal projections, the peptide and... 

Preterm labour is the major cause of perinatal morbidity and mortality. Oxytocin antagonists offer an attractive approach to prevention. Chapter 7 reviews three decades of medicinal chemistry in this field. The peptide approach has resulted in valuable injectable products. Selectivity over the related vasopressin receptors and improvement in pharmacokinetic profile have been the key challenges for more recent non-peptide programmes, and these seem likely to yield orally available medicines. 

The Maillard reaction is likely to take on additional significance with the introduction of many new protein and peptide pharmaceuticals. For example, Tarelli et al. have demonstrated that lysine vasopressin undergoes rapid glycation in the presence of reducing sugars in both aqueous and solid formulations and that the N-terminal adduct can form rapidly even at — 20°C [52], A textbook that deals with the consequences for the chemical and life sciences of the Maillard reaction has been published [53]. 

The residues required for internalization, like those implicated in desensitization motifs, do not always meet the requirements for putative sites of kinase-mediated phosphorylation. Among the numerous motifs that have been implicated, an NPXXY motif (154,173) may be required for agonist-induced activation and inter-nahzation of the p -adrenergic receptor, and a dileucine motif in the carboxyl tail of many GPCRs (154) may be involved in internalization of receptors such as the Pj-adrenergic (174) and the vasopressin Via receptors (175). 

ADH, a nonapeptide, released from the posterior pituitary gland promotes re-absorption of water in the kidney. This response is mediated by vasopressin receptors of the V2 subtype. ADH enhances the permeability of collecting duct epithelium for water (but not for electrolytes). As a result, water is drawn from urine into the hyperosmolar inter-stitium of the medulla. Nicotine augments (p. 110) and ethanol decreases ADH release. At concentrations above those required for antidiuresis, ADH stimulates smooth musculature, including that of blood vessels ( vasopressin ). The latter response is mediated by receptors of the Vi subtype. Blood pressure rises coronary vasoconstriction can precipitate angina pectoris. Lypres-sin (8-L-lysine vasopressin) acts like ADH. Other derivatives may display only one of the two actions. 

Bale TL, Contarino A, Smith GW, Chan R, Gold LH, Sawchenko PE, Koob GF, Vale WW, Lee KF (2000) Mice deficient for corticotropin-releasing hormone receptor-2 display anxiety-like behaviour and are hypersensitive to stress. Nat Genet 24 410-414 Bale TL, Picetti R, Contarino A, Koob GF, Vale WW, Lee KF (2002) Mice deficient for both corticotropin-releasing factor receptor 1 (CRFRl) and CRFR2 have an impaired stress response and display dichotomous anxiety-like behavior. J Neurosci 22 193-199 Barberis C, Tribollet M (1996) Vasopressin and oxytocin receptors in the central nervous system. Grit RevNeurobiol 10 119-154... 

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