The role of adenosine 3',5'-cyclic monophosphate (cAMP) in the release of noradrenaline from central neurones has been investigated by examining the effects of forskolin, 3-isobutyl-l-methylxanthine (IBMX), cis-6-(p-acetamidophenyl)-1,2,3,4,4a, 10b-hexahydro-8,9-dimethoxy-2-methyl-benzo[c] [1,6]-naphthyridine bis (+ +hydrogenmaleinate) (AH21-132; a new phosphodiesterase inhibitor) and N6,O2'-dibutyryl-adenosine 3',5'-cyclic monophosphate (dibutyryl-cAMP) on the outflow of tritiated compounds from rat and rabbit cerebral cortex slices preincubated with [3H]-noradrenaline. Forskolin, IBMX, AH21-132 and dibutyryl-cAMP produced a concentration-dependent increase in both basal and electrically-evoked efflux of tritium from rat and rabbit cortex slices. The increase in basal tritium efflux from rabbit cortex slices elicited by forskolin and IBMX could be attributed mainly to an increase in [3H]-DOPEG although a small increase in [3H]-noradrenaline was also observed. Forskolin and (when combined with noradrenaline) IBMX and AH21-132 increased the cAMP content of rat cortex slices at similar or somewhat higher concentrations that they increased tritium efflux. Neither forskolin nor IBMX or AH21-132 had any effect on the cocaine-sensitive uptake of [3H]-noradrenaline into synaptosomes prepared from rat or rabbit cortex. The effects of forskolin, IBMX and dibutyryl-cAMP on electrically-evoked overflow of tritium from rat and rabbit cortex slices were reduced when cocaine (10 microM) was present in the superfusion medium, although forskolin produced a similar increase in cAMP in the absence or presence of cocaine. It is suggested that cAMP may facilitate the normal process of noradrenaline release by nerve stimulation.

1 Postsynaptic a-adrenoceptors in rat isolated aortic strips and portal veins have been examined using a number of agonist and antagonist drugs which have varying selectivity for a1-and a2-adrenoceptors. 4 In portal veins, the order of potency of the antagonists was prazosin> BE2254 > phentolamine > yohimbine > rauwolscine, again indicating an al-type of receptor. 5 The mean pA2 value for yohimbine was not significantly different in either tissue. However, mean pA2 values for prazosin, BE-2254 and phentolamine were approximately one order of magnitude lower in portal veins than in aortic strips, suggesting that the receptors in the two tissues may not be identical.

No abstract