Antagonism inhibitory sites

In this variant of insurmountable antagonism, the antagonist acts by combining with a separate inhibitory site on the receptor macromolecule. Agonist and antagonist molecules can be bound at... 

If we apply the law of mass action to this form of antagonism, the proportion of inhibitory sites occupied by the antagonist will be given by the Hill-Langmuir equation ... 

Phenothiazines and analogs - Bradley, et al..have proposed a neuronal basis for the central action of CPZ (1) At sites where NA is an excitatory transmitter, CPZ is antagonistic (2) at inhibitory sites, there is no antagonism, but neuronal depression occurs by other mechanisms such as inhibition of uptake of NA by nerve terminals. The Increase of brain phosphatase activity brought about by CPZ may result from the unmasking of normally masked sites of phosphatase action and may have importance in the behavioral effects of CPZ.60 Elevation of melatonin in the tissues is a... 

The elimination of y-BHC symptoms by avermectin may be explained as follows The primary action site of y-BHC is likely to involve the picrotoxinin receptor (5). Therefore, one could assume that y-BHC, at least in part, acts in an identical manner to picrotoxinin which has already been shown to antagonize the action of avermectin Kass et al. (29) reported two types of avermectin action on the nervous system of the nematode, based on the inhibition by picrotoxinin. One is the avermectin-induced blockage of interneuron-excitatory motorneuron transmission, which can be reversed by picrotoxinin. The other is the avermectin-induced blockage of the transmission between inhibitory motoneurons and muscle, which cannot be reversed by picrotoxinin. 

There is, however, some preclinical basis to justify the use of 5-HT,d receptor antagonists in the treatment of depressive disorders. It has been known for some time that facilitation of 5-HT neurotransmission can be achieved by blockade of the presynaptic reuptake site by selective serotonin reuptake inhibitors such as paroxetine and fluoxetine and that such an action results in clinically useful antidepressant properties. It is now believed that the concentration of 5-HT at the terminal is controlled not only by the uptake site but also by an inhibitory terminal 5-HT autoreceptor (see Figure 1) which in higher species of animals is likely to be of the S-HTm subclass (see earlier in this chapter). This inhibitory 5-HT autoreceptor is normally activated by the endogenous release of 5-HT and antagonism of this receptor would lead to disinhibition of the neurone and a facilitation of 5-HT release. Since the net effect of this action would be to provide a rapid increase in 5-HT release, it has been postulated that a 5-HTn, receptor antagonist could have antidepressant properties. 

When the catalytic and regulatory subunits are dissociated, the catal3rtic activity, measured with saturating concentrations of carbamyl phosphate, displays conventional hyperbolic kinetics with respect to aspartate concentration. However, sigmoidal kinetics are shown by the native aspartate carbamyltransferase, in which form the subunits are associated. In the presence of CTP, the sigmoidicity of the rate-aspartate curve is further increased, with the effect that the apparent Michaelis constant for aspartate is increased. ATP competes with CTP for the regulatory site, with the result that the CTP inhibitory effect is antagonized. 

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