Pharmacology calmodulin

In addition, vinpocetine selectively inhibits a specific calcium, calmodulin-dependent cycHc nucleotide phosphodiesterase (PDF) isozyme (16). As a result of this inhibition, cycHc guanosine 5 -monophosphate (GMP) levels increase. Relaxation of smooth muscle seems to be dependent on the activation of cychc GMP-dependent protein kinase (17), thus this property may account for the vasodilator activity of vinpocetine. A review of the pharmacology of vinpocetine is available (18). 

The role of calcium in regulating cardiovascular physiology is presented in the fourth section of this volume. House et al. have provided an excellent review on the structure of calmodulin-dependent protein kinase II and its role in the contractility as well as proliferation and migration of VSMC. Banderali et al. have examined in detail the cellular regulation and pharmacological properties of calcium-activated potassium channels and their role in control of vascular tone by endothelium. 

Moriguchi S (2011) Pharmacological study on Alzheimer s drugs targeting calcium/ calmodulin-dependent protein kinase II. J Pharmacol Sci 117(1) 6-11... 

Cyclosporine provides maintenance immunosuppression by inhibition of the activation of T lymphocytes via a multifaceted mechanism. The drug, a fat soluble 11 amino acid cyclic polypeptide, crosses the lymphocyte membrane freely where it forms a pharmacologically active complex with the intracellular immunophilin receptor cyclophilin. This complex, but not cyclosporine by itself, inhibits the Ca /calmodulin-activated form of serine/threonine phosphatase calcineurin, thereby inhibiting the activation of NFAT cells. The latter action is considered to be the key step... 

While the first four chapters focus on the membrane calcium channels, the next two explore the intracellular compartment. Dr. Brostrom and his colleagues review present-day knowledge about the intracellular calcium receptor, calmodulin, while the Editors contribute an update on the basic and applied pharmacology of a novel class of intracellular calcium antagonists, the methylenedioxyindenes. 

Cyclic AMP is catabolized to 5 -adenosine monophosphate by the enzyme cyclic nucleotide phosphodiesterase, which terminates any further cAMP-initiated reactions. This enzyme also requires Mg + for activity. Calcium, again in consort with calmodulin, can stimulate phosphodiesterase activity. Phosphodiesterase appears to exist in multiple forms, each with specificity toward different substrates. Calcium and calmodulin activate only one form of the enzyme. The enzyme is potently inhibited by methyl xanthines, such as caffeine, theophylline, and theobromine. It is believed that at least part of the pharmacological effects of such compounds can be explained through their inhibition of phosphodiesterase and the consequent reduction in the catabolism of cAMP. 

For those interested in the pharmacology of calmodulin antagonists or physicochemical studies on calmodulin structure, Vincenzi (1981) and Krebs (1981) are suggested. Reviews that include substantial sections on the adenylate cyclase-phosphodiesterase systems and calmodulin or on calmodulin-dependent protein phosphorylations can be found in Cheung (1981), Brostrom and Wolf (1981), and Stoclet (1981). 

Thus, the individual pharmacological effects exerted by each calcium channel blocker may depend upon the extent to which the drug affects other intracellular systems as well as its potency at the calcium channel. Many of the effects described here would tend to increase the vasodilator action of the drugs, such as inhibition of calmodulin-dependent enzymes. However, these other effects are subsidiary to blockade of the calcium channel, as they occur mainly at concentrations higher than those required to block the channels therefore, at low concentrations the actions of the calcium channel blocking drugs are relatively specific. 

The pyrrolo[2,3-J]pyrimidine skeleton is often encountered in important pharmacologically active substances, and more recently it has been observed in a class of marine natural products known as rigidins. These alkaloids have been obtained from tunicates obtained near Okinawa and New Guinea and they have been shown to exhibit very significant calmodulin antagonist activities. Gupton s... 

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