Catecholamine stimulatory

This group consists of j3-adrenergic receptor blockers, the antiarrhythmic activity of which is associated with inhibition of adrenergic innervation action of the circulatory adrenaline on the heart. Because all 8-adrenoblockers reduce stimulatory sympathetic nerve impulses of catecholamines on the heart, reduce transmembrane sodium ion transport, and reduce the speed of conduction of excitation, sinoatrial node and contractibility of the myocardium is reduced, and automatism of sinus nodes is suppressed and atrial and ventricular tachyarrhythmia is inhibited. 

Corticosteroids also affect adrenomeduUary function by increasing epinephrine production the mechanism is exertion of a stimulatory action on two of the enzymes that regulate catecholamine synthesis, tyrosine hydroxylase, the rate-Umiting enzyme, and phenyl-ethanolamine Af-methyltransferase, which catalyzes the conversion of norepinephrine to epinephrine. Steroids also influence the metabolism of circulating catecholamines by inhibiting their uptake from the circulation by noimeuronal tissues (i.e., extraneuronal uptake see Chapter 9). This effect of corticoids may explain their permissive action in potentiating the hemodynamic effects of circulating catecholamines. 

The effects of catecholamines are mediated by cell-surface receptors. Adrenoceptors are typical G protein-coupled receptors (GPCRs see Chapter 2). The receptor protein has an extracellular N-terminus, traverses the membrane seven times (transmembrane domains) forming three extracellular and three intracellular loops, and has an intracellular C-terminus (Figure 9-1). G protein-coupled receptors are coupled by G proteins to the various effector proteins whose activities are regulated by those receptors. Each G protein is a heterotrimer consisting of a, 3, and 7 subunits. G proteins are classified on the basis of their distinctive ct subunits. G proteins of particular importance for adrenoceptor function include Gs, the stimulatory G protein of adenylyl cyclase Gj and G0, the inhibitory G... 

The role of cyclic AMP as modulator of prolactin secretion was first suggested by the finding of a stimulatory effect of cyclic AMP derivatives (17-22) and inhibitors of cyclic nucleotide phosphodiesterase activity such as theophylline and IBMX (22-26) on the secretion of this hormone. More convincing evidence supporting a role of cyclic AMP in the action of dopamine on prolactin secretion had to be obtained, however, by measurement of adenohypophysial adenylate cyclase activity or cyclic AMP accumulation under the influence of the catecholamine. As illustrated in Fig. 1, addition of 100 nM dopamine to male rat hemipituitaries led to a rapid inhibition of cyclic AMP accumulation, a maximal effect (30% inhibition) being already obtained 5 min after addition of the catecholamine. Thus, while dopamine is well known to stimulate adenylate cyclase activity in the striatum (27, 28), its effect at the adenohypophysial level in intact cells is inhibitory. Dopamine has also been found to exert parallel inhibitory effects on cyclic AMP levels and prolactin release in ovine adenohypophysial cells in culture (29) and purified rat mammotrophs (30). Using paired hemipituitaries obtained from female rats, Ray and Wallis (22) have found a rapid inhibitory effect of dopamine on cyclic AMP accumulation to approximately 75% of control. 

As Illustrated in Fig. 7, 3 yM CRF and 1 yM (-)Isoproterenol cause a 190 and 110% stimulation of adenylate cyclase activity In rat pars intermedia particulate fraction, respectively. An additive effect Is observed when both stimulatory agents are present. Dopamine (30 yM), on the other hand, has no significant effect alone. However, In the presence of GXP, the catecholamine causes a 40 to 60% Inhibition of adenylate cyclase activity stimulated by CRF, ISO or CRF + ISO. It can also be seen that while 0.3 mM GXP alone causes a 100% increase In basal adenylate cyclase activity, it leads to a marked potentiation of the effect of ISO and CRF on [ 2P] cyclic AMP accumulation. It should be noticed that In the absence of the guanyl nucleotide, dopamine has no Inhibitory effect on adenylate cyclase activity In any of the groups studied. 

The fresh leaves of the khat shrub (Catha edulis) are chewed by several millions of people in East Africa and the Arabian peninsula for their euphoric and stimulating properties (284). The rather newly discovered alkaloid cathinone [(S)-a-aminopropiophenone] is responsible for the stimulating properties of khat (284). It has been shown that cathinone induces release at physiological catecholamine storage sites in a manner similar to that of amphetamine. Further results suggest that cathinone and amphetamine produce their stimulant effects via the same dopaminergic mechanism (599). The more recently discovered khat constituents merucathinone, merucathine, and pseudomerucathine were found to have only weak dopamine-releasing effects and were therefore considered unlikely to play an important role in the stimulatory actions of khat leaves (414). 

Actions Dobutamine [doe BYOO ta meen] is a synthetic, direct-acting catecholamine that is a ( -receptor agonist. It is available as a racemic mixture. One of the stereoisomers has a stimulatory activity. It increases cardiac rate and output with few vascular effects. 

All catecholamine receptors are metabotropic. They act by initiating metabohc processes affecting cellular functions. P-adrenergic receptors, receptors for epinephrine, and norepinephrine act by stimulatory G proteins to increase cAMP in the post-synaptic cell. cAMP binds to and activates protein-kinase enzyme. 

Epinephrine. Epinephrine (Adrenalin) finds use in a number of situations because of its potent stimulatory effects on both a- and /3-adrcncrgic receptors. Like the other catecholamines, epinephrine is light sensitive and easily oxidized on exposure to air because of the catechol ring system. The development of a pink to brown color indicates oxidative breakdown. To minimize oxidation, solutions of the drug are. stabilized by the addition of reducing agents such as sodium bisulfite. As the free amine, it is used in aqueous solution for inhalation. Like other amines, it forms salts with acids, for example, those now used include the hydrochloride and the bitartratc. Epinephrine is destroyed readily in alkaline solutions and by metals (c.g.. Cu, Fe, Zn), weak... 

P-Adrenergic receptors (P-ARs) are members of the superfamily of G protein-coupled receptors (GPCRs) that are stimulated by the catecholamines epinephrine and norepinephine (1). P-ARs have been shown to play important roles in the regulation of cardiovascular, respiratory, metabolic, central nervous system, and reproductive functions by the sympathetic nervous system. Three distinct subtypes of P-ARs have been identified and cloned Pj, P2, and P3 (2-4). All three P-ARs are believed to signal by coupling to the stimulatory G protein Gsa, leading... 

Refsnes M, Thoresen GH, Sandnes D, Dajani OF, Dajani L, Christoffers T. Stimulatory and inhibitory effects of catecholamines on DNA synthesis in primary rat hepatocyte cultures role of oq- and [1-adrenergic mechanisms. J Cell Physiol 1992 151 164-171. 

Stimulatory effect of catecholamines on NGF synthesis would lead to an unstable positive feedback mechanism, since higher NGF concentrations would drive catecholamine synthesis. 

Furukawa, Y., Furukawa, S., Ikeda, F., Satoyoshi, E. and Hayashi, K. (1986b) Aliphatic side chain of catecholamine potentiates the stimulatory effect of the catechol part on the synthesis of nerve growth factor. FEES Lett. 208 258-262. 

The natural synthetic pathway of these neurotransmitters begins with phenylalanine, an essential amino acid that converts into tyrosine. In turn, tyrosine boosts levels of dopamine and norepinephrine. Phenylalanine is found in protein-dense foods such as eggs, soy, nuts, and animal products. Phenylalanine and tyrosine are also available as nutritional supplements, and are sometimes used in that form for the stimulatory, antidepressing effects mediated by the catecholamine neurotransmitters. When used in this way, they should be taken with vitamin C and B complex supplements (which can be... 

Asano,T., Pedersen, S. E., Scott, C. W and Ross, E. M. (1984) Reconstitution of catecholamine-stimulated binding of guanosine 5 -0-(3-thiotriphosphate) to the stimulatory GTP-binding protein of adenylate cyclase. Biochemistry 23,5460-5467... 

Increased intracellular Ca2+ activity also activates secretory cells (25). Inhibition studies Indicate that the Inotropic effect of monensln Is mediated In part by the release of catecholamines from the adrenals and/or the heart Itself (22). Ifonensln also discharges catecholamines from disaggregated bovine chromaffin cells In culture (26.27), and Induces the release of acetylcholine at the neuromuscular jxmctlon (28). Thus, the secretion stimulatory activity of monensln also supports the concept that Increased Intracellular Na" " activity produces a rise in intracellular Ca2+ activity sufficient to stimulate Ca2+-activable cells. 

Many new data have supported a role for catecholamines in analgesia and the abstinence syndrome. Stimulation of brain catecholamine biosynthesis by morphine can be Inhibited by narcotic antagonists and tolerance develops to this stimulatory effect. ... 

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