Basic & Clinical Pharmacology (LANGE Basic Science) 10th by Bertram Katzung

By Bertram Katzung

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While the five established mechanisms do not account for all the chemical signals conveyed across cell membranes, they do transduce many of the most important signals exploited in pharmacotherapy. Intracellular Receptors for Lipid-Soluble Agents Several biologic ligands are sufficiently lipid-soluble to cross the plasma membrane and act on intracellular receptors. One class of such ligands includes steroids (corticosteroids, mineralocorticoids, sex steroids, vitamin D), and thyroid hormone, whose receptors stimulate the transcription of genes by binding to specific DNA sequences near the gene whose expression is to be regulated.

This is not the case with an irreversible (or noncompetitive) antagonist, which reduces the maximal effect the agonist can achieve, although it may not change its EC50 . The concentration (C') of an agonist required to produce a given effect in the presence of a fixed concentration ([I]) of competitive antagonist is greater than the agonist concentration (C) required to produce the same effect in the absence of the antagonist. The ratio of these two agonist concentrations (the "dose ratio") is related to the dissociation constant (Ki ) of the antagonist by the Schild equation: Pharmacologists often use this relation to determine the K i of a competitive antagonist.

Elevated cytoplasmic Ca 2+ concentration promotes the binding of Ca2+ to the calcium-binding protein calmodulin, which regulates activities of other enzymes, including calcium-dependent protein kinases. Figure 2–14. The Ca2+ -phosphoinositide signaling pathway. Key proteins include hormone receptors (R), a G protein (G), a phosphoinositide-specific phospholipase C (PLC), protein kinase C substrates of the kinase (S), calmodulin (CaM), and calmodulin-binding enzymes (E), including kinases, phosphodiesterases, etc.

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