Receptor occupancy increases

We can now consider how quickly occupancy rises after the ligand is first applied, at time zero (tl = 0). Receptor occupancy is initially 0, so that p1 is 0. Thereafter, occupancy increases steadily and will be denoted pAR(l) at time t ... 

The experiment of Figure 1.7 points to the same conclusion. When very low concentrations of histamine are applied in the presence of a relatively large fixed concentration of impromidine, the overall response is mainly due to the receptors occupied by impromidine however, the concentration-response curves cross as the histamine concentration is increased. This is because the presence of impromidine reduces receptor occupancy by histamine (at all concentrations) and vice versa. When the lines intersect, the effect of the reduction in impromidine occupancy by histamine is exactly offset by the contribution from the receptors occupied by histamine. Beyond this point, the presence of impromidine lowers the response to a given concentration of histamine. In effect, it acts as an antagonist. Again, the implication is that the partial agonist can combine with all the receptors but is less able to produce a response. 

In some circumstances CR1 and CR3 may efficiently bind their ligands, but phagocytosis may not be initiated. As described above, pretreatment with PMA may increase the ability of neutrophils to ingest these bound particles. Several naturally-occurring molecules can also promote the ingestion of coated particles presumably, this is achieved via alterations in the efficiency of coupling of receptor occupancy to intracellular signalling systems. 

Effects of increasing doses of atropine on heart rate (A) and salivary flow (B) compared with muscarinic receptor occupancy in humans. The parasympathomimetic effect of low-dose atropine is attributed to blockade of prejunctional muscarinic receptors that suppress acetylcholine release. 

Some patients who take clozapine take another neuroleptic drug, and the consequences of this practice in terms of prolactin have been studied in five patients (758). After the addition of haloperidol (4 mg/day) to clozapine the mean prolactin concentration increased from 9.7 ng/ml to 16 ng/ml at week 4 and 19 ng/ml at week 6. Each subject had an increase in the percentage of D2 receptor occupancy, and the group mean increased from 55% at baseline to 79% at week 4 the increased prolactin concentrations correlated with receptor occupancy. 

Kapur S, Roy P, Daskalakis J, Remington G, Zipursky R. Increased dopamine D(2) receptor occupancy and elevated prolactin level associated with addition of haloperidol to clozapine. Am J Psychiatry 2001 158(2) 311 1. 

Effects of increasing doses of atropine on heart rate (A) and salivary flow (B) compared with muscarinic receptor occupancy in humans. The parasympathomimetic effect of low-dose atropine is attributed to blockade of prejunctional muscarinic receptors that suppress acetylcholine release. (Modified and reproduced, with permission, from Wellstein A, Pitschner HF Complex dose-response curves of atropine in man explained by different functions of Mi and M2 cholinoceptors. Naunyn Schmiedebergs Arch Pharmacol 1988 338 19.)... 

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