Second messengers function

Tissue sensitivity Alterations in receptor number Alterations in receptor affinity Alterations in second-messenger function Alterations in cellular and nuclear responses Patients are "more sensitive or "less sensitive to an agent... 

Newman ME, Drummer D, Lerer B Single and combined effects of desimipramine and lithium on serotonergic receptor number and second messenger function in rat brain. J Pharmacol Exp Ther 252 826-831, 1990 Newman ME, Lerer B, Lichtenberg P, et al Platelet adenylate cyclase activity in depression and after clomipramine and lithium treatment. Psychopharmacology 109 231-234, 1992... 

A cyclic InsP3 has also been found in several tissues. This isomer is an extremely labile compound and can be rapidly metabolised to InsP3 by phosphodiesterases [24], It is not known whether it has any second messenger function but it appears to be present in only very small amounts. Inositol phosphates containing four, five and six phosphates have been isolated from stimulated tissues [25-27], There is likely... 

Hannun, YA (1994) The sphingomyelin cycle and the second messenger function of ceramide. Journal of Biological Chemistry, 269, 3125-3128. 

Studies from this laboratory have been focused on GM3 and sialosylparaglobo-side (SPG), two fundamental gangliosides present in a great variety of extra-neural tissues and cells. We have observed two distinct functions of these compounds and their derivatives (1) control of transmembrane signaling or second messenger function and (2) modulation of cell-cell interaction or cell adhesion. This research area has been reviewed many times previously (Hakomori, 1984, 1987, 1990, 1993 Bremer and Hakomori, 1984 Hakomori et al., 1990 Hakomori and Igarashi, 1993). The reader should refer to these earlier reviews in conjunction with this chapter. 

It is now known that the initial event following binding of the agonist to its receptor (usually within 30 secs) is a rapid hydrolysis of phosphatidylinositol bisphosphate by a specific phospholipase C. This produces inositol 1,4,5-triphosphate and diacylglycerol, both of which have second messenger functions. 

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). 

Nitric Oxide. Nitric oxide [10102-43-9] NO, is a ubiquitous intracellular and intercellular messenger serving a variety of functions including vasodilation, cytotoxicity, neurotransmission, and neuromodulation (9). NO is a paramagnetic diatomic molecule that readily diffuses through aqueous and hpid compartments. Its locus of action is dictated by its chemical reactivity and the local environment. NO represents the first identified member of a series of gaseous second messengers that also includes CO. 

Pseudohypoparathyroidism is characterized by end-organ resistance to parathyroid hormone (98,108). This disease takes various forms, including Albright s hereditary osteodystrophy, which has unusual physical features and a generalized resistance to G-protein-linked hormones that function through cAMP as a second messenger. This defect is associated with a deficiency in the levels of the a-subunit of (109). Because this defect may be generalized, such patients also have olfactory dysfunction (110). 

Depletion of ATP in the cells prevents maintenance of the membrane potential, inhibits the functioning of ion pumps, and attenuates cellular signal transduction (e.g., formation of second messengers such as inositol phos phates or cyclic AMP). A marked ATP depletion ultimately impairs the activ-itv of the cell and leads to ceil death. 

Ca2+ is an important intracellular second messenger that controls cellular functions including muscle contraction in smooth and cardiac muscle. Ca2+ channel blockers inhibit depolarization-induced Ca2+ entry into muscle cells in the cardiovascular system causing a decrease in blood pressure, decreased cardiac contractility, and antiarrhythmic effects. Therefore, these drugs are used clinically to treat hypertension, myocardial ischemia, and cardiac arrhythmias. 

Cyclic nucleotides (cAMP and cGMP) are formed enzymatically from the corresponding triphosphates. As ubiquitous second messengers, they mediate many cellular functions which are initiated by first (extracellular) messengers. Their prime targets in eucaryotic cells are protein kinases ( cyclic AMP-dependent protein kinase, cyclic GMP-dependent protein kinase), ion channels and ensymes. 

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