No description available.

In the studies described in this thesis the ability of muscarinic and ?1-adrenoceptor, as well as depolarising stimuli to initiate phosphoinositide metabolism in various regions of rat brain were examined. Furthermore, the ability of these stimuli to initiate phosphoinositide hydrolysis in developing brain was observed. Both muscarinic and ?1-adrenoceptor-induced phosphoinositide hydrolysis have marked regional distributions in rat brain. This regional distribution of functional responsiveness seems to correlate reasonably well with measurements of known receptor density. It is also clear that there is no variability in the coupling of both of these receptors in rat brain, thus implying a relationship between the functional responses and receptor occupancy. Pirenzepine appears to be able to differentiate between muscarinic receptor-induced phosphoinositide responses in the hindbrain from those in the forebrain regions. Both elevated K+ and veratrine can initiate phosphoinositide hydrolysis in rat brain. The regional responses to elevated K+ seem, at least, in part to be due to transmitter release, although a role for voltage-sensitive Ca++ channels in such responses is indicated by the effects produced by dihydropyridine Ca++ channel antagonists and activators. Muscarinic and ?1-adrenoceptors show different developmental patterns of phosphoinositide responsiveness. The ?1-adrenoceptor seems to be more efficiently coupled during the first two weeks of postnatal development whereas the muscarinic receptor shows no variability in coupling. Instead, carbachol produces supramaximal responses in young rats. Lithium also potentiates [3H]-InsP1 and [3H]-InsP2 accumulations more in young rats. Moreover lithium produces a time-dependent inhibition of [3H]-InsP3 and [3H]-InsP4 in both young and adult rats. Physostigmine produces no enhancement of the response to elevated K+ in young rats. Furthermore, brain slices from young rats seem to be more sensitive to the Ca++ channel activator BAY-K8644. The significance of these results are discussed in the text.