Considering Enhancer Receptors

For a trial aiming to explain the striking sensitivity difference of the cultured cortical cells of rats and chickens towards (-)-BPAP see Sect. 3.4.1. 

In order to get direct evidence for (-)-BPAP-sensitive receptors, we performed experiments with [3H]-(-)-BPAP. Unfortunately, we were unable to find unequivocal evidence for the predicted binding sites for [3H]-(-)-BPAP. Furthermore, the explanation of the peculiar bell-shaped concentration/effect curve characteristic of the enhancer effect of (-)-BPAP (see Fig. 3.11) remains to be understood. 

Because we were unable to find, using [3H]-(-)-BPAP, direct evidence for specific enhancer receptors, we tried to approach the problem from another angle. In the rat brain, using a classic pharmacological method, we found convincing indirect evidence for (-)-BPAP-sensitive enhancer receptors in the mesencephalon (Knoll et al. 2002a). 

The subcutaneous administration of 1 mg/kg tetrabenazine depletes the catecholamine stores in the brain within 1 h. As a consequence of this change, tetrabenazine treatment inhibits the acquisition of a two-way avoidance reflex 

The concurrent administration of 1 mg/kg 3-F-BPAP with 0.1 mg/kg (-)-BPAP significantly inhibited the enhancer effect of (-)-BPAP, but 1 mg/kg 3-F-BPAP did not influence the enhancer effect of 1 mg/kg (-)-BPAP (Fig. 2 in Knoll et al. 2002a). This is a clear indication that the compounds bind to the same receptor, to which (-)-BPAP has a much higher affinity than 3-F-BPAP. 

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To determine quantitatively how the response of the signalling system varies with the pattern of periodic stimulation, it is useful to consider first the total amount of intracellular cAMP, Pj, synthesized above the basal level over a period once a constant amplitude has been reached in response to pulsatile stimulation (dashed area in fig. 8.16). How this quantity varies with the duration Ti and interval To is shown in fig. 8.17. At very large values of To the response increases and later saturates as the duration of stimulation increases. At lower values of Tq, the response passes through a maximum as Ti rises the increase in response due to prolonged stimulation is indeed counterbalanced by enhanced receptor desensitization. 

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