Receptors negative-feedback processes

Because baroreceptors respond to stretch or distension of the blood vessel walls, they are also referred to as stretch receptors. A change in blood pressure will elicit the baroreceptor reflex, which involves negative feedback responses that return blood pressure to normal (see Figure 15.6). For example, an increase in blood pressure causes distension of the aorta and carotid arteries, thus stimulating the baroreceptors. As a result, the number of afferent nerve impulses transmitted to the vasomotor center increases. The vasomotor center processes this information and adjusts the activity of the autonomic nervous system accordingly. Sympathetic stimulation of vascular smooth muscle and the heart is decreased and parasympathetic stimulation of the heart is increased. As a result, venous return, CO, and TPR decrease so that MAP is decreased back toward its normal value. 

Phosphorylation of the P-adrenergic receptor by PARK, like its phosphorylation by the cAMP-dependent enzyme, represents an example of negative feedback. However, unlike phosphorylation by cAMP-dependent protein kinase, phosphorylation by PARK represents an example of homologous desensitization only the P-adrenergic receptor would be affected in this process and, moreover, only those receptor molecules occupied by ligand would be affected. 

Negative Feedback. Some of the neurotransmitter diffuses back to the surface of the nerve cell that released it. There are also receptors that tit the neurotransmitter here. When a neurotransmitter binds a receptor (called an autoreceptor) at the axon terminal of the nerve cell that released it, it tells the nerve cell that there s plenty of neurotransmitter already in the synapse. So don t release anymore This process is called negative feedback and is analogous to the way a thermostat works in your home to control room temperature. 

The nervous system has several properties in common with the endocrine system, which is the other major system for control of body function. These include high-level integration in the brain, the ability to influence processes in distant regions of the body, and extensive use of negative feedback. Both systems use chemicals for the transmission of information. In the nervous system, chemical transmission occurs between nerve cells and between nerve cells and their effector cells. Chemical transmission takes place through the release of small amounts of transmitter substances from the nerve terminals into the synaptic cleft. The transmitter crosses the cleft by diffusion and activates or inhibits the postsynaptic cell by binding to a specialized receptor molecule. In a few cases, retrograde transmission may occur from the postsynaptic cell to the presynaptic neuron terminal. 

G. Integration of Autonomic Function Functional integration in the autonomic nervous system is provided mainly through the mechanism of negative feedback. This process utilizes modulatory pre- and postsynaptic receptors at the local level and homeostatic reflexes at the systemic level. 

Clot formation takes about 5 min depending on the size and position of the wound after which it is necessary to stop the process. Switching off the production of fibrin is achieved by negative feedback, i.e. inactivation of the activated factors. Thrombin, the last protease in the cascade, binds to a receptor protein known as thrombomodulin present on the endothelial wall of the blood vessels. This alters the thrombin so that it can no longer activate fibrinogen but instead activates another vitamin K-dependent serine protease known as Protein C. This, in the presence of Ca and a protein cofactor, binds to a phospholipid membrane and forms a complex which inactivates Factors V and Vllg both of which are needed for the production of thrombin. 

Receptor theory is based on the classical Law of Mass Action as developed by Michaelis and Menten (20) for the study of enzyme catalysis. The extrapolation of classical enzyme theory to receptors is, however, an approximation. In an enzyme-substrate (ES) interaction, the substrate S undergoes an enzyme-catalyzed conversion to a product or products. Because of the equilibrium established, product accumulation has the ability to reverse the reaction process. Alternatively, the latter can be used in other cellular pathways and is thus removed from the equilibrium situation or can act as a feedback modulator (21) to alter the ES reaction either positively or negatively (Equation 10.2). 

Fxmctional models were later generated to predict tumor growth in terms of cell kinetics and/or cell-cell interactions. More importantly, these models allow for the incorporation of growth inhibition and stimulation by autocrine (tumor-derived), paracrine (microenvironment), or humoral/exogenous mediators. While the mathematical derivation of these relationships is beyond the scope of this chapter, it clearly represents an effort to model receptor-mediated processes, auto-stimulation, negative and positive feedback loops, and dynamic processes between competing subpopulations of... 

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