Adrenergic response, modulation

Danner S, Lohse MJ (1999) Regulation of p-adrenergic receptor responsiveness modulation of receptor gene expression. Rev Physiol Biochem Pharmacol 136 183- 223... 

Other authors showed that (R)a-methylhistamine, together with the inotropic and chronotropic adrenergic response from transmurally-stimulated atrial preparations, also inhibits the release of noradrenaline, thus providing direct evidence that histamine H3-receptors negatively modulate the cardiac sympathetic activity at a presynaptic site of action (Endou et al., 1994). In addition, it was demonstrated that (R)a-methylhistamine, at concentrations greater than 1 pM, produces further antiadrenergic activity by acting at inhibitory presynaptic a.2-adrenoceptors. This result is supported by the fact that yohimbine reverses this effect. 

The modulation of the N-type Ca2+ channels has been shown for some presynaptic receptors to be the mechanistic basis for the inhibition of Ca2+ influx [29]. In 1989 Takemura et al. [30] reported on the effective inhibition of histamine release from rat hypothalamic slices by the N-type Ca2+ -channel blocker ca-conotoxin. In addition Endou et al. [23] showed that to-conotoxin greatly potentiated the modulatory effect of (R)a-methylhistamine on cardiac adrenergic responses. Yang and Hatton [31] provided direct evidence for an H3 receptor-mediated modulation of ion permeability of neurons. They showed that in magnocellular histaminergic neurons from the rat posterior hypothalamus, H3... 

Chu CP, Kunitake T, Kato K, et al. The a1D-adrenergic receptor modulates cardiovascular and drinking responses to central salt loading in mice. Neurosci Lett 2004 356 33-36. 

Our findings indicate that in resistance vessels NO attenuates adrenergic responses by a postjunctional action, but not by decreasing NE release. In the heart NO does not modulate the chronotropic response to adrenergic nerve stimulation, but does enhance NE overflow in association with coronary vasodilation and ischemia/reperfusion. 

Vanhoutte PM, Cooke JP, Lindblad LE, Shepherd JT, Flavahan NA. Modulation of postjunctional alpha-adrenergic responsiveness by local changes in temperature. Clin Sci (Lond) 68(Suppl 10), 121s-123s, 1985. 

Gross, S. S., Guo, Z. G., Levi, R., Bailey, W. H., and Chenouda, A. A., 1984, Release of histamine by sympathetic nerve stimulation in the guinea pig heart and modulation of adrenergic responses—a physiological role for cardiac histamine Circ. Res. 54 516-526. 

Because of the possible implication of PEA as one of the adrenergic ergotropic modulators, alterations in its disposition may be responsible for the euphoric effects of A -THC in man . Acute administration of 3 mg/kg of A -THC increased l -fold the brain levels of PEA and daily administration of 0.3 mg/kg for 8 days doubles PEA brain levels. In contrast A -THC induces only relatively small changes in the brain levels of serotonin, catecholamines and acetylcholine. 

The general picture of muscle contraction in the heart resembles that of skeletal muscle. Cardiac muscle, like skeletal muscle, is striated and uses the actin-myosin-tropomyosin-troponin system described above. Unlike skeletal muscle, cardiac muscle exhibits intrinsic rhyth-micity, and individual myocytes communicate with each other because of its syncytial nature. The T tubular system is more developed in cardiac muscle, whereas the sarcoplasmic reticulum is less extensive and consequently the intracellular supply of Ca for contraction is less. Cardiac muscle thus relies on extracellular Ca for contraction if isolated cardiac muscle is deprived of Ca, it ceases to beat within approximately 1 minute, whereas skeletal muscle can continue to contract without an extraceUular source of Ca +. Cyclic AMP plays a more prominent role in cardiac than in skeletal muscle. It modulates intracellular levels of Ca through the activation of protein kinases these enzymes phosphorylate various transport proteins in the sarcolemma and sarcoplasmic reticulum and also in the troponin-tropomyosin regulatory complex, affecting intracellular levels of Ca or responses to it. There is a rough correlation between the phosphorylation of Tpl and the increased contraction of cardiac muscle induced by catecholamines. This may account for the inotropic effects (increased contractility) of P-adrenergic compounds on the heart. Some differences among skeletal, cardiac, and smooth muscle are summarized in... 

Most interesting in this light are our initial experiments on mouse bladder showing the absolute dependence of [i adrenergic relaxation in the bladder to the presence of PLB. Isoproterenol or forskolin activation of the A -kinase pathway led to complete relaxation of bladder from wild type mice, with little or no response in the PLB knockout bladder (K. Nobe R. J. Paul, unpublished observations). On the other hand, relaxation via G -kinase pathway activation was identical in the PLB knockout and wild-type bladder. PLB modulation of SR appears to be the dominant pathway for A-kinase mediated relaxation in mouse bladder in contrast to its lesser role in this pathway for the vascular tissues studied. 

Early evidence that prejunctional histamine H3-receptors may modulate the sympathetic nerve activity on the heart was provided by Luo et al., (1991). These authors clearly stated that the selective H3-agonist (R)a-methylhistamine attenuates the inotropic response induced by transmural stimulation of the adrenergic nerve terminals in the isolated right atrium, without affecting basal contractile force of the preparation or the positive inotropic effect elicited by exogenous noradrenaline. The effect of (R)a-methylhistamine, which is not modified by Hi and H2-receptor blockade, was reversed by the specific H3-receptor antagonist thioperamide, at concentrations which do not influence the inhibitory activity mediated by other presynaptic receptors, like a2-adrenoceptors. 

Kubista H, Boehm S (2006) Molecular mechanisms underlying the modulation of exocytotic noradrenaline release via presynaptic receptors. Pharmacol Ther 112 213 12 Lakhlani PP, MacMillan LB, Guo TZ, McCool BA, Lovinger DM, Maze M, Limbird LE (1997) Substitution of a mutant a2A-adrenergic receptor via hit and run gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo. Proc Natl Acad Sci USA 94 9950-5... 

Collins, S., Caron, M.G., and Lefkowitz, R.J. 1991. Regulation of adrenergic receptor responsiveness through modulation of receptor gene expression. Annu. Rev. Physiol. 53 497-508. 

It is well documented that coordinated myocyte handling of Ca2+ is essential for efficient excitation-contraction coupling in the heart. Since cardiac pump is able to alter its function in response to any requirement in the body and the regulation of contractile function of individual myocytes obtained by modulation of intracellular Ca2+ signaling, the characteristics of regulation induced by adrenergic stimulations are very important for maintaining the normal heart function in humans. 

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