Abstract
A recent study carried out by this laboratory demonstrated that exogenous histamine increases the somatostatin (SS) receptor/effector system in the rat frontoparietal cortex (Puebla and Arilla, 1995). In the present study we examined the participation of the H2-histaminergic system in this modulation by use of the H2-receptor agonist and antagonist dimaprit and cimetidine, respectively. Dimaprit administration [20 μg/rat, intracerebroventricularly (ICV)] to rats 2 hours before decapitation increased the number of SS receptors in the frontoparietal cortex without changing the affinity constant. Pretreatment with cimetidine (20 μg/rat, ICV) prevented the dimaprit-induced changes in SS binding in the frontoparietal cortex, whereas cimetidine alone (20 μg/rat, ICV) had no observable effect on this parameter. The in vitro addition 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 forskolin (FK)-stimulated adenylyl cyclase (AC) activity in frontoparietal cortex membranes from dimaprit-treated rats than in controls, an effect that was prevented by pretreatment with cimetidine. No significant differences, however, were detected for the basal or FK-stimulated AC enzyme activity in the control, dimaprit-, and/or cimetidine-treated groups, which suggests no impairment of the AC catalytic subunit. In addition, the functional activity of the guanine nucleotide-binding inhibitory protein Gi, as measured by the capacity of the stable GTP analogue 5′-guanylylimidodiphosphate [Gpp(NH)p] to inhibit FK-stimulated AC activity, was not altered by dimaprit. Thus, the increased SS-mediated inhibition of AC activity observed in the dimaprit-treated rats may be caused by the increase in the number of SS receptors. Neither dimaprit nor cimetidine affected somatostatinlike immunoreactivity (SSLI) content. The present results, together with the fact that SS and histamine have been shown to influence locomotor activity and nociception in a similar manner, suggest that some of the neurotransmitter effects of SS may be modulated by histamine via H2-histaminergic receptors.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Puebla, L., Arilla, E. Effect of Dimaprit and Cimetidine on the Somatostatinergic System in the Rat Frontoparietal Cortex. Neuropsychopharmacol 14, 367–374 (1996). https://doi.org/10.1016/0893-133X(95)00149-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1016/0893-133X(95)00149-8