Agonist-receptor interaction

FIGURE 1.5 Schematic diagram of response production by an agonist. An initial stimulus is produced at the receptor as a result of agonist-receptor interaction. This stimulus is processed by the stimulus-response apparatus of the cell into observable cellular response. 

The concept of spare receptors is very useful clinically because it allows one to think precisely about the effects of drug dosage without needing to consider biochemical details of the signaling response. The of the agonist-receptor interaction... 

The Kd of the agonist-receptor interaction determines what fraction (B/Bmax) of total receptors will be occupied at a given free concentration (C) of agonist regardless of the receptor concentration ... 

Agonist/Receptor Interactions and Signal Transduction Pathways in Ischemic Preconditioning... 

The initial high levels of IP3 in response to agonist-receptor interaction are not maintained during the sustained phase of contraction (Chilvers et al, 1989 Chilvers and Nahorski, 1990). IP3 fells to baseline levels within a minute of the onset of contraction. I(1,4,5)P3 is metabohzed by two pathways, both of which are activated by increases in cytosolic Ca " hydrolysis by a 5-phosphatase enzyme to I(1,4)P2, or phosphorylation to I(1,3,4,5)P4 and subsequent hydrolysis to its inactive isomer I(1,3,4)P3 (Chilvers and Nahorski, 1990). No physiological role for I(1,3,4,5)P4 has yet been identified in airway smooth muscle, although in other cells evidence exists that I(1,3,4,5)P4 may modulate plas-malemmal Ca ion channels (Irvine and Moor, 1986). The only phosphoinositide metabolite which has been shown to release stored Ca in ASM is I(1,4,5)P3. 

Temussi, P.A., Lelj, F., Tancredi, T., Castiglione-Morelli, M.A., and Pastore, A. (1984). Soft agonist-receptor interactions, theoretical and experimental simulation of the active site of the receptor site of sweet molecules, hit. J. Quantum Chem. 26,889-906. 

Haddad, E. B., Landry, Y., Gies, J. P. Sialic acid residues as catalysts for M2-muscarinic agonist receptor interactions. Mol. Pharmacol. 1990, 37, 682-688. 

Ca + mobilized in response to membrane stimuli is derived from either intra- or extracellular sources (Figure 2). Membrane Ca + channels mediating Ca2+ entry have been classified into two major types (18-20). Receptor-operated channels (ROC, Figure 2) are associated with membrane receptors and are activated by specific agonist-receptor interactions, whilst potential-dependent channels (PDC, Figure 2) are activated by membrane depolariza-... 

Conformational Effects of Fluorine Substitution. Mechanisms considered to explain adrenergic selectivities of fluorinated norepinephrine (and related adrenergic agonists) have included 1) an indirect effect of the C-F bond on the conformation of the ethanolamine side-chain or 2) a direct effect of the C-F bond on agonist-receptor interaction. In the first formulation, proposals were made that fluorine situated in a position ortho (position 2 or 6) to the ethanolamine side chain creates a bias for side chain conformations favorable for binding to p- and a-adrener-gic receptors, respectively. 

The first four chapters and Chapter 6 are connected with 3D molecular descriptors and their uses for QSAR and molecular similarity studies associated with molecular modeling of agonist-receptor interactions, with drug design, and with the discovery of new lead compounds for various types of biological activities. 

The receptors of this family possess an intrinsic enzymatic activity (tyrosine-kinase or guanylate-cyclase) activated following the agonist-receptor interactions. 

Fig. 28.5 Dose-response curves for agonist-receptor interaction depicting binding, several intermediate steps and the final measured response A represents a tissue response, B and C intermediate events and D agonist binding.

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