EFFECT OF DIMAPRIT AND CIMETIDINE ON THE SOMATOSTATINERGIC SYSTEM IN THE RAT FRONTOPARIETAL CORTEX

A recent study carried out by this laboratory demonstrated that exogen ous histamine increases the somatostatin (SS) receptor/effector system in the rat frontoparietal cortex (Puebla and Arilla, 1995). In the pr esent study we examined the participation of the H-2-histaminergic sys tem in this modulation by use of the H-2-receptor agonist and antagoni st dimaprit and cimetidine, respectively. Dimaprit administration [20 mu g/rat, intracerebroventricularly (ICV)] to rats 2 hours before deca pitation increased the number of SS receptors in the frontoparietal co rtex without changing the affinity constant. Pretreatment with cimetid ine (20 mu g/rat, ICV) prevented the dimaprit-induced changes in SS bi nding in the frontoparietal cortex, whereas cimetidine alone (20 mu g/ rat ICV) had no observable effect on this parameter. The in vitro addi tion of dimaprit or cimetidine to frontoparietal cortex membranes from untreated rats did not markedly affect the SS binding characteristics . Somatostatin caused a significantly higher inhibition of basal and f orskolin (FK)-stimulated adenylyl cyclase (AC) activity in frontoparie tal cortex membranes from dimaprit-treated rats than in controls, an e ffect that was prevented by pretreatment with cimetidine. No significa nt differences, however, were detected for the basal or FK-stimulated AC enzyme activity in the control, dimaprit-, and/or cimetidine-treate d groups, which suggest no impairment of the AC catalytic subunit. In addition, the functional activity of the guanine nucleotide-binding in hibitory protein G(i), as measured by the capacity of the stable GTP a nalogue 5'-guanylylimidodiphosphate [Gpp(NH)p] to inhibit FK-stimulate d AC activity, was not altered by dimaprit. Thus, the increased SS-med iated inhibition of AC activity observed in the dimaprit-treated rats may be caused by the increase in the numbers of SS receptors. Neither dimaprit nor cimetidine affected somatostatinlike immunoreactivity (SS LI) content. The present results, together with the fact that SS and h istamine have been shown to influence locomotor activity and nocicepti on in a similar manner, suggest that some of the neurotransmitter effe cts of SS may be modulated by histamine via H-2-histaminergic receptor s.