Drug-induced release of biogenic amines from synaptosomes and blood platelets of guinea-pigs

Abstract

Synaptosomes from guinea-pig brain were compared with blood platelets (partly from previous experiments) regarding the action of imipramine, the benzoquinolizine derivative Ro 4-1284, tyramine and p-chlormethamphetamine (PCMA) on the contents of stored radio-labelled 5-hydroxytryptamine (5HT), dopamine (DA) and noradrenaline (NA). Normal and reserpinized preparations were used in order to differentiate between granular and extragranular (reserpine-resistant) sites. Imipramine, in concentrations greater than those inhibiting 5HT- and NA-uptake released the three amines from granular and extragranular sites and showed the same order of potency in synaptosomes as in platelets. The drug Ro 4-1284 acted on the granular amines only, but its action on NA was less potent in synaptosomes than in platelets. Tyramine and PCMA also caused an exclusive release of granular amines in synaptosomes, whereas in platelets the drugs released extragranular 5HT (and DA) as well as the granular amines. Tyramine was more potent in synaptosomes than in platelets, and PCMA showed a preferential effect on 5HT in synaptosomes but not in platelets. It is concluded that, regarding the action of monoamine-releasing drugs, platelets are only partial models for synaptosomes. However, they may be superior to synaptosomes in predicting the pattern of amine release in brain in vivo as seen with Ro 4-1284.