Regulatory Influence

The smooth muscle cell does not respond in an all-or-none manner, but instead its contractile state is a variable compromise between diverse regulatory influences. While a vertebrate skeletal muscle fiber is at complete rest unless activated by a motor nerve, regulation of the contractile activity of a smooth muscle cell is more complex. First, the smooth muscle cell typically receives input from many different kinds of nerve fibers. The various cell membrane receptors in turn activate different intracellular signal-transduction pathways which may affect (a) membrane channels, and hence, electrical activity (b) calcium storage or release or (c) the proteins of the contractile machinery. While each have their own biochemically specific ways, the actual mechanisms are for the most part known only in outline. 

Fur has a regulatory influence on the acid-shock response in E. coli and Salmonella. The acid-response reactions are important for the cells to survive when they pass the acidic gut. In Salmonella, a Fur-dependent, but iron-independent, regulation of acid-response genes is observed. Certain point mutations of Fur (e.g. H90R) do not respond to iron, but are able to regulate an acid-response gene (Foster, 2000). Unfortunately, the functions of the Fur-dependent gene products in acid response are not known. 

Lower cortisol levels in the face of normal ACTH levels can reflect a relatively decreased adrenal output. Yet under circumstances of classic adrenal insufficiency, there is usually increased ACTH release compared to normal levels. Thus, in PTSD there may be an additional component of feedback on the pituitary that is acting to depress ACTH levels, making them appear normal. Indeed, elevations in ACTH would be expected not only from a reduced adrenal output but also from increased CRF stimulation (Baker et al. 1999 Bremner et al. 1997). On the other hand, the adrenal output in PTSD may be relatively decreased, but not substantially enough to affect ACTH levels, hi any event, the normal ACTH levels in PTSD in the context of the other findings suggest a more complex model of the regulatory influences on the pituitary in this disorder than reduced adrenal insufficiency. 

Light is a major regulatory influence on carotenoid synthesis in many plant and microbial systems. A review of this photoregulation has been published. Other papers report the photoinduction of the biosynthesis of phytoene and other carotenoids in strains of Neurospora crassa. " ... 

Fig. 3.1. Principal mechanisms of intercellular communiciation. a) communication via extracellular messengers and receptor systems, b) communication via gap junctions. Gap junctions are direct connections between cells. They are coated by proteins (drawn as circles) that can have a regulatory influence on the transport, c) communication via cell surface proteins.

A common feature of the different adenylyl cyclases is the stimulation of their enzyme activity by the GTP-bound form of the a-subimit of the Gs-protein. Furthermore, all subtypes are stimulated by the diterpene forskolin. In addition to the central regulation by the activated a-subunit, there are other stimulatory or inhibitory influences on the different subtypes of adenylyl cyclase, in a manner characteristic for the particular subtype. The various subtypes differ in these regulatory influences, whereby none of the different subtypes have an identical pattern of regulation. 

In addition to regulation by cAMP, protein kinase A is also subject to other regulatory influences. Thus, the C subunit may be specifically phosphorylated (see 7.2.1). It is not clear, however, which protein kinase is responsible for phosphorylation of the C suhunit. 

Structure and function of the cell formations of higher organisms are highly dependent on adhesive interactions based on direct cell-cell contact and on interactions of cells with the extracellular matrix. Adhesion between cells and with the extracellular matrix has a regulatory influence on migratory behavior, proliferation and differentiation of an individual cell within the cell formation. The adhesion processes thus do not only serve to simply hold cells together in the formation. They also have a regulatory effect... 

Mountford, D.O. and Pybus, V., Regulatory influences on the production of gamma-aminobutyric acid by a marine Pseudomonas, Appl. Environ. Microbiol., 58, 237, 1992. 

For a number of overt, broad spectrum immunosuppressive xenobiotics (e.g., azathioprine) there is sufficient clinical experience to indicate the types of neoplasms for which there is an increased risk. These tumor types are listed in Table 27.1. Also listed are the tumors that occur in the unfortunate experiment of nature, namely patients infected with human immunodeficiency virus type 1 (HIV-1) and the tumors that may occur at higher incidence with more selective yet strong immunosuppressants (e.g., cyclosporin, sirolimus, and tacrolimus). Compared to the broad spectrum immunosuppressive agents listed above, most IMBPs express a highly selective regulatory influence on the immune system modulating the activity of host defense systems rather than mediating frank immunosuppression. 

Although we have access to an enormous amount of information, the quality and reproducibility of data varies considerably. Governmental and regulatory influences have not provided any guarantees as to the accuracy of data related to xenobiotics and the researcher needs to understand the purpose and mandates behind an information resource to fully evaluate the data contained within. For example, the National Institute for Occupational Safety and Health (NIOSH) Registry of Toxic Effects of Chemical Substances (RTECS) criteria for selection of data is not based on the reproducibility of that data. Other sources, such as the National Library of Medicine s Hazardous Substances Databank (HSDB), present information compiled from a wide variety of source materials that are extensively reviewed by experts. 

The inhibitory spiny GABAergic neurons send projections by two major pathways whose net effect appears to exert balanced regulatory influences on the ascending thalamo- cortical circuits that mediate control of voluntary movement through the descending corticospinal projections to the spinal ventral-horn motoneurons that innervate skeletal muscles. A widely accepted, but tentative model of the basic anatomical connections of this complex is summarized schematically in Fig. 12.1(12,15,17-20). 

D8. Drahota, Z., and Gutmann, G., Long-term regulatory influence of the nervous system on some metabolic differences in muscles of different function. Physiol. Bohemoslov. 12, 339-348 (1963). 

The role of regulatory bodies has been important in encouraging industries to adopt cleaner production strategies. Regulatory influences include international agreements and government legislation at the federal, state, and local levels. 

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