Regulatory influence of histamine receptor activation and inhibition on the synthesis and level of hypothalamic histamine

Abstract

The blockade of histamine receptors by repeated i.p. administration of 10-20 mg/kg of chloropyramine and tripelennamine, the potent H1-receptor antagonists, or by the i.c.v. administration of 2 mg/kg of metiamide and cimetidine, the highly selective H2-receptor antagonists, led to significant enhancement in the hypothalamic HD2(L-histidine carboxylase; EC 4.1.1.22.) activity and the histamine content; whereas the activation of the histamine H1-receptor by 4 mg/kg i.e.v. doses of 2-pyridylethylamine, the specific histamine H1 agonist, resulted in significant diminution in both the synthesis and level of this amine. These compounds either do not influence the hypothalamic HD in vitro or cause opposite effects in relatively high concentrations. After repeated administration of either agonists or antagonists, no significant alteration have been observed in the hypothalamic HNMT (histamine-N-methyl-transferase; EC 2.1.1.8.) activity. There were, however, two exceptions: 2 mg/kg i.c.v. doses of 2-methylhistamine and 4-methylhistamine produced remarkable inhibitions in the hypothalamic HNMT activity. These effects do not seem to correspond to the agonistic character of the compounds, but mask the indirect actions and create difficulties in the discovery of regulatory events. The regulatory influence which suppresses or stimulates the basal activity of HD under the activation or the inhibition of the functional state of histamine receptor, is assumed to be mediated through the cyclic AMP system.

Regulation of histidine decarboxylase activity in rat hypothalamusin vitro by ATP and cyclic AMP: Enzyme inactivation under phosphorylating conditions

“…In any case, the observation that cAMP, in combination with ATP inhibits HD activity, is in accord with the finding that the stimulation of HA receptors elevates the activity of HA-sensitive adenylate cyclase [3][4][5] and elicits an inhibition on HA synthesis [2]. However, we know no other enzyme, except ornithine decarboxylase (L-ornithine carboxylase, EC 4.1.1.17) and S-adenosylmethionine decarboxylase (S-adenosylmethionine carboxylase EC 4.1.1.50) [14], whose inactivation is preceded by an increase in cAMP concentration and activation of cAMP-dependent protein kinase.…”

“…Our previous studies showed the regulatory influence of histamine receptor agonists and antagonists on the synthesis and level of hypothalamic histamine and suggested the possible involvement of cyclic nucleotides in this action [1][2]. Previous and recent evidence that HA and its agonists stimulate the production of cAMP in different brain regions, including hypothalamus [3][4][5], have further strengthened the reality of this conception.…”

Uptake, metabolism, and release of [3H]‐histamine by glial cells in primary cultures of chicken cerebral hemispheres

“…Table 1 also shows the effects of HA-related agents on HA transport. The HI agonist 2-me-HA and the H,-agonist 4-me-HA (Ganellin, 1982) with remarkable HNMT-blocking activity (Huszti and Magyar, 1984) produced partial inhibitions of the uptake. In the range of 1-100 pM, a linear relationship was found between the percentage of inhibition and the logarithm of concentration of the latter compounds up to 60%, resulting in ICs0 values of 2 pM and 5 pM, respectively.…”