Download Cyclic Nucleotides: Part II: Physiology and Pharmacology by J. H. Exton (auth.), Dr. John W. Kebabian, Professor Dr. PDF

By J. H. Exton (auth.), Dr. John W. Kebabian, Professor Dr. James A. Nathanson (eds.)

Cyclic nucleotides are in detail inquisitive about the implications of both stimulation or blockade of receptors; consequently, an realizing of the biochemistry of cyclic nucleotides needs to be vital for pharmacologists. Pharmacology is a technology that between different issues investigates chemical substances that have an effect on the body structure of cells, tissues and organs. usually pharmacologists account for the influence of low concentrations of a drug upon a tissue through invoking the presence of a receptor upon the outside of the telephone. conventional pharmacologists excelled at picking and classifying the houses of receptors. A. J. CLARK'S monograph within the prior sequence of the guide of Experimental Pharmacology (CLARK 1937) summarized the math underlying the normal pharmacological strategy in the direction of receptors. via its nature, although, vintage pharmacology supplied little worthy information regarding the intracellular occasions happening due to occupying a receptor; for instance, ALQUIST (1948) pointed out the beta-adrenocep­ tor, yet he didn't offer any perception into how stimulation of the receptor produces tissue-specific physiological responses. the invention of cyclic AMP by way of RALL and SUTHERLAND (see RALL, Vol. I) ended in biochemical investigations of many various receptors (including ALQUIST'S beta-adrenoceptor) that proportion a cyclic nucleotide as a standard think about the biochemical mechanisms that translate the occupancy of receptors into physiological results. Ten years in the past, within the advent to their monograph on cyclic nucleotides, ROBISON et al. (1971) commented at the quick development of curiosity in cyclic nucleotides over the previous years.

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Extra resources for Cyclic Nucleotides: Part II: Physiology and Pharmacology

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Thus the possibility that glucagon activation of liver phosphorylase is partly due to inhibition of phosphorylase phosphatase has yet to be proved. H. EXTON 7. Evidence Against a Role for Ca2+ in Glucagon Stimulation of Glycogenolysis Several investigators (FRIEDMANN and PARK 1968; KEPPENS et al. 1977; ASSIMACOPOULOS-JEANNET et al. 1977; BLACKMORE et al. 1978; 1979b, CHEN et al. 1978; FoDEN and RANDLE 1978) have shown that high concentrations of glucagon alter Ca 2 + fluxes in the perfused rat liver and isolated rat hepatocytes, and some workers have proposed that these changes are related to certain actions of the hormone on hepatic metabolism (FRIEDMANN and RASMUSSEN 1970; CHEN et al.

C. Regulation of Hepatic Gluconeogenesis I. Glucagon Stimulation of Hepatic Gluconeogenesis 1. Evidence That Glucagon Exerts Physiological Control on Gluconeogenesis Experiments in vivo in which physiological levels of glucagon have been replaced in animals infused with somatostatin have demonstrated that glucagon exerts physiological control on hepatic gluconeogenesis (JENNINGS et al. 1977; CHERRING- lH. D :: c c a a c o U o~--~----~----~~--~~--~~~ -40 0 240min Fig.

G. high blood glucose and insulin levels and low glucagon levels, the liver may release lac- Regulation of Carbohydrate Metabolism by Cyclic Nucleotides 25 tate formed by glycolysis. In this situation, glucagon's action would be thought of as inhibiting glycolysis, as originally proposed by SCHIMASSEK and MITZKAT (1963). As will be discussed in Sect. 5, this effect is probably attributable to inhibition of pyruvate kinase and P-fructokinase. 2. Glucagon Inhibition of Hepatic Pyruvate Kinase Many mechanisms have been suggested for the stimulatory effect of glucagon on hepatic gluconeogenesis (for references, see PILKIS et al.

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