Activity spontaneous

The determination and evaluation of potentiodynamic curves can only be used as a preliminary assessment of corrosion behavior. The protection current requirement and the limiting value for the potential control can only be determined from so-called chronopotentiostatic experiments as in DIN 50918. in systems that react with spontaneous activation after the protection current is switched off or there is a change in the operating conditions, quick-acting protection current devices must be used. Figure 8-6 shows the circuit diagram for such a potentiostat. 

The extended ternary complex model can take into account the phenomenon of constitutive receptor activity. In genetically engineered systems where receptors can be expressed in high density, Costa and Herz [2] noted that high levels of receptor expression uncovered the existence of a population of spontaneously active receptors and that these receptors produce an elevated basal response in the system. The relevant factor is the ratio of receptors and G-proteins (i.e., elevated levels of receptor cannot yield constitutive activity in the absence of adequate amounts of G-protein, and vice versa). Constitutive activity (due to the [RaG] species) in the absence of ligand ([A] = 0) is expressed as... 

The observation that receptors can demonstrate spontaneous activity necessitated elements of ion two-state theory to be incorporated into receptor theory. 

The extended ternary complex model [23] was conceived after it was clear that receptors could spontaneously activate G-proteins in the absence of agonist. It is an amalgam of the ternary complex model [12] and two-state theory that allows proteins to spontaneously exist in two conformations, each having different properties with respect to other proteins and to ligands. Thus, two receptor species are described [Ra] (active state receptor able to activate G-proteins) and [RJ (inactive state receptors). These coexist according to an allosteric constant (L = [Ra]/[Ri]) ... 

Constitutive receptor activity, receptors spontaneously produce conformations that activate G-proteins in the absence of agonists. This activity, referred to as constitutive activity, can be observed in systems in which the receptor expression levels are high and the resulting levels of spontaneously activating receptor species produce a visible physiological response. An inverse agonist reverses this constitutivie activity and thus reduces, in a dose-dependent... 

Fields et al. [67] first demonstrated evolution of bradykinin in HAE plasma even if an initiating surface is absent indicating seemingly spontaneous activation of the kinin-forming cascade in the absence of this control protein. This work also disproved... 

Spontaneous interaction of F-actin and myosin alone (spontaneous activation of myosin ATPase by F-actin Yes No... 

Fig. 4.1 Hypothetical model of pathogenesis of pain in DSP. (1) Injury of peripheral nerve fibers due to multifocal inflammation and secreted macrophage activation products results in abnormal spontaneous activity of neighboring uninjured nociceptive fibers ( peripheral sensitization ). (2) Furthermore, the aberrant inflammatory response in DRG leads to alterations in neuronal sodium and calcium channel expression and ectopic impulse generation. (3) This results in central remodeling within the dorsal horn due to A-fiber sprouting and synaptic formation with pain fibers in lamina 11, and maintenance of neuropathic pain ( central sensitization ). Reproduced with permission from (Keswani et al. 2002)...

Figure 7.5 Rate recording of the dose-dependent inhibitory effects of apomorphine (pg/kg) on the spontaneous activity of a neuron in the medial prefrontal cortex of the halothane anaesthetised rat and its antagonism by haloperidol (HAL, 0.5mg/kg). Time scale is 50 min intervals. Reproduced by permission from Dailey (1992)...

Dailey, JW and Webster, RA (1993) Dopamine-like effects of clozapine on spontaneously active neurons in the rat prefrontal cortex. J. Psychopharm. 1 A7. 

Figure 4.7 Changes in intraceiiuiar calcium in cultured rat ventricular myocytes exposed to oxidant stress. Calcium was measured using the fluorescent probe Fura>2. The ratio of the Fura-2 fluorescence measured at 340 and 380 nm excitation is shown and this is proportional to the intracellular calcium concentration. The fast-speed traces shown (note the 3.5 s time-scale) were recorded after various durations of oxidant stress. Myocytes under control conditions (before t = 0) show spontaneous calcium transients. These transients decreased in frequency with oxidant stress until cells failed to show spontaneous activity but continued to maintain a low intracellular calcium.

General procedures for mouse behavioural experiments are described in Reference [141], SA = spontaneous activity TF = tail flick RT = rectal temperature. 

Tables 6.8-6.11 illustrate the wide range of C3 side-chain modified A -THC analogues that have been reported in the literature, together with associated in vitro and in vivo data. The affinity of classical cannabinoid analogues for the CBi receptor has been shown to correlate with depression of spontaneous activity and the production of antinociception, hypothermia and catalepsy in mice, and with psychomimetic activity in humans [93]. However, in some cases, there were unexplained differences between the observed trends in binding affinity and the trends in activity in mouse behavioural models. This may point to differences in efficacy among full agonists, partial agonists and antagonists/inverse agonists, or may reflect differences in in vivo metabolism or blood-brain barrier penetration or a combination of these factors.

Smit, M. J., Leurs, R., Alewijnse, A. E. et al. (1996). Inverse agonism of histamine H2 antagonist accounts for upregulation of spontaneously active histamine H2 receptors. Proc. Natl. Acad. Sci. USA 93, 6802-7. 

Blackburn T., Suzuki K, Ashby C., Jr. (2006). The acute and chronic administration of the 5-HT (2B/2C) receptor antagonist SB-200646A significantly alters the activity of spontaneously active midbrain dopamine neurons in the rat an in vivo extracellular single cell study. Synapse. 59, 502-12. 

Electrophysiological properties of histaminergic neurons show spontaneous activity of about 2 Hz. A combination of sodium, calcium and potassium conductances account... 

We could detect no changes in [Ca2+]L during spontaneous transients, consistent with the conclusions drawn above. Indeed, we found that if SR Ca2+ was elevated, then spontaneous activity was suppressed until SR Ca2+ levels returned to their initial value. This is also consistent with SR activity inhibiting rather than potentiating [Ca2+]j and force. 

Bolton But these are single cells, they are not resting. If you look at the membrane potentials they are very likely to be active. If you don t voltage clamp them, they can be spontaneously active. 

There are only two reports of the human evaluation of a 6-hydroxylated N,N-dialkyltryptamine. Szara and Hearst (223) studied the effects of 6-hydroxy-N,N-diethyltryptamine (6-OH-DET 56) in a single subject. Doses of 1 and 2 mg were inactive a 5-mg dose produced a short-lasting perceptual disturbance and a 10-mg dose, after 1 hr, produced some psychotomimetic disturbances. Rosenberg et al. (182) compared the activity of DMT with that of 6-OH-DMT (55) in five human subjects. While DMT was active, the 6-hydroxy derivative was found to be inactive at intramuscular doses of approximately 50 to 75 mg. At a dose of 10 mg/kg, 6-OH-DMT (55) increased spontaneous activity in mice more so than a comparable dose of DMT 6-OH-DET (36) was essentially equiactive with DET in this respect (224). In most other animal studies, however, 6-hydroxylation of DMT has been observed to result in a decrease or complete loss of behavioral activity (228,236-238). The behavioral potency of 5-OMeDMT (59) was also reduced by 6-hydroxylation (226). 7-Hydroxy-N,N-dimethyltrypt-amine (7-OH-DMT 57) has not been evaluated in man. At an intraperitoneal dose of 33 jtM/kg, 7-OH-DMT displayed no behavioral effects in rats (228). The pharmacologic effects of all four hydroxylated derivatives of DMT, psilocin (49), bufotenine (53), 6-OH-DMT (55), and 7-OH-DMT (57) have been compared in studies by Taborsky et al. (228) and by Cerletti et al. (29). 

The fact that most serotonergic dorsal raphe neurons are dependent on extrinsic excitatory or facilitatory inputs to express their characteristic spontaneous activity may seem to contradict previous studies suggesting that these neurons may function as autonomous pacemakers (42) with an endogenous rhythm (31) attributable to the presence of pacemaker potentials (8). Such a contradiction exists only if one insists that endogenous rhythms and pacemaker potentials must, by definition, be totally autonomous, i.e., completely independent of all extrinsic synaptic or neurohumoral influences. Such a definition would seem too restrictive in view of the fact that some invertebrate neurons display pacemaker potentials only when certain afferent fibers are stimulated (38) or when exposed to certain neurohumoral substances (18,28). 

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