Antagonistic effects of growth hormone-releasing factor and somatostatin on brain histamine

Studies on the morphological distribution of histamine (HA)-secreting neurons and their hypothalamic projections suggest that HA may play a key role in regulating neuroendocrine functions, some of which have been recently elucidated. To investigate possible interactions between the somatotropinergic and histaminergic systems in the brain, the effects of GRF-44 [0.1-10 micrograms intracerebroventricular (icv)] and somatostatin (SS-14; 0.1-10 micrograms, icv) on HA in five different parts of the hypothalamo-hypophyseal system, and in the hippocampus and frontal cortex, were studied using a highly sensitive HPLC system for determination of HA. GRF-44 (1 microgram, icv) elicited significant (P less than 0.005) increases in the concentration of HA in the anterior hypothalamus, posterior hypothalamus, median eminence, adenohypophysis, neurohypophysis, frontal cortex, and, to a lesser extent, in the hippocampus, after a clear time-dependent pattern with maxima 15 min after injection. In contrast, SS-14 (1 microgram, icv) significantly (P less than 0.005) decreased the levels of HA in all areas studied, except in the neurohypophysis. The SS-induced HA levels reached minima 30 min after injection. The antagonistic effects of GRF-44 and SS-14 on the release of brain HA were dose dependent, showing an inverse linear correlation within the range 0.1-10 micrograms in the anterior hypothalamus (r = -0.59) and posterior hypothalamus (r = -0.75). Responses of HA to GRF-44 and SS-14 (range: 0.1-10 micrograms) also exhibited an inverse linear correlation in the median eminence (r = -0.90) and adenohypophysis (r = -0.58), while in the hippocampus and frontal cortex the antagonistic effects of GRF and SS displayed an inverse curvilinear correlation. SS-14 ED50 values ranged from 0.6 to 1.75 nmol with Emax of 0.65-6.10 nmol. GRF-44 ED50 values ranged from 0.02-0.3 nmol and the Emax values oscillated between 0.2 and 1.90 nmol in the regions studied. The greatest responses of HA to GRF-44 and SS-14 were obtained in the hypothalamo-hypophyseal system. Although brain HA is present in both the neuronal and the mast cell compartments, changes induced in the concentration of HA by centrally administered GRF-44 and SS-14 appear to occur mostly in the neuronal compartment. Therefore, it is likely that the somatotropinergic and histaminergic systems reciprocally interact at the central level to regulate still unknown neuroendocrine functions.