Cellular Transduction

At low stimulus intensities about 25% of the pheromone molecules adsorbed on the antenna elicit nerve impulses of the receptor neuron (Kaissling 1987). Modeling reveals that - besides the 17% enzymatically rapidly degraded molecules - more than half of the molecules adsorbed must be lost due to the - still hypothetical - odorant deactivation on the hairs (Kaissling 2001). The 25% fraction of effective molecules was determined by radiometric measurements and by counting the nerve impulses at low stimulus intensities such that about one nerve impulse is elicited per receptor neuron by a one-s stimulus (3x10-10 g of bombykol/f.p.). At and below this stimulus intensity one pheromone molecule is sufficient to elicit a nerve impulse (Kaissling and Priesner 1970). 

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Serotonin (5-HT) produces a rapid elevation of superoxide that stimulates the mitogenesis of bovine pulmonary artery smooth muscle cells (SMCs). EGb scavenges superoxide elevated by 5-HT, hence preventing 5-HT-induced mitogenesis on both SMCs and Chinese hamster lung fibroblasts. These results indicate that EGb inhibits the cellular transduction signaling process that leads to mitogenesis, as a result of its antioxidant activity [141]. 

Balmoralmycin (232), isolated from Streptomyces sp. strain P6417, displays an inhibitory activity against protein kinase C (IC50 50 M), an important enzyme in context with cellular transduction mechanisms [165]. Structurally, 232 is nearly identical with the antifungal antibiotic C104 (197) [153], which lacks an oxygen... 

Moncada, S. (1993). The L-arginine nitric oxide pathway, cellular transduction and immunological roles. Adv. Second Messenger Phosphoprotein Res. 28, 97-99. 

The spatial and steric requirements for high affinity binding to protein kinase C (PKC), a macromolecule that has not yet been crystallized, were determined. Protein kinase C plays a critical role in cellular signal transduction and is in part responsible for cell differentiation. PKC was identified as the macromolecular target for the potent tumor-promoting phorbol esters (25). The natural agonists for PKC are diacylglycerols (DAG) (26). The arrows denote possible sites of interaction. 

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. 

The regulation of the total peripheral resistance also involves the complex interactions of several mechanisms. These include baroreflexes and sympathetic nervous system activity response to neurohumoral substances and endothelial factors myogenic adjustments at the cellular level, some mediated by ion channels and events at the cellular membrane and intercellular events mediated by receptors and mechanisms for signal transduction. As examples of some of these mechanisms, there are two major neural reflex arcs (Fig. 1). Baroreflexes are derived from high-pressure barorecep-tors in the aortic arch and carotid sinus and low-pressure cardiopulmonary baroreceptors in ventricles and atria. These receptors respond to stretch (high pressure) or... 

Small ubiquitous calcium-binding protein. Calmodulin binds and regulates the activity of many protein targets involved in cellular signal transduction pathways mediated by calcium. Calmodulin is ranked among the most conserved proteins and plays a key role in many cellular processes. 

Pharmocodynamic tolerance develops in response to continued application of drugs, by mechanisms that include reversible cellular adaptation processes, such as receptor desensitization, internalization and downregu-lation as well as changes in the activity and levels of other components of the receptor s signal transduction pathways. 

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