Histaminergic Neuromodulation of the Release of Vasopressin

Abstract

In an attempt to clarify the nature of histaminergic neuromodulation of the vasopressinergic system, several studies under different experimental paradigms were carried out. L-Histidine loads (8 mmol/kg, i.p.) induced a marked increase in histamine (HA) in the anterior (AHR) and posterior (PHR) hypothalamic regions, the median eminence (ME) and adenohypophysis (Ah) with no apparent effect on the concentration of HA in the neurohypophysis (Nh), as measured by high-performance liquid chromatography. These findings correlated with decreases in vasopressin (VP) levels in the AHR and ME, accompanied by increases of the neuropeptide in the PHR and Ah. Intraperitoneal injections of HA (6 µmol/kg), resulted in a significant (p < 0.005) rise in VP levels in the PHR, ME and Ah. HA induced an elevation of VP in the prefrontal cortex (PFC) from 6.23 ± 2.02 to 43 ± 4.05 µU/mg, as well as a 60% reduction in neurohypophyseal VP. These HA-induced VP responses were abolished by both mepyramine (3 µmol/kg) and famotidine (4 µmol/kg) in the PHR and PFC. Mepyramine suppressed the HA-induced VP response in the Ah and enhanced it in the Nh, while famotidine did the opposite. When alpha-fluoromethylhistidine (FMH), an irreversible inhibitor of histidine decarboxylase, was administered at doses of 100 mg/kg/day (i.p.), hypothalamic HA levels fell by 40–45% after 1 h, by 50% after 3 h, and by 65–80% after 24 h in adrenalectomized rats. In the same conditions, but after a week of treatment with FMH, the VP response to adrenalectomy was clearly impaired. These results seem to demonstrate that the physiological levels of neuronal HA are indispensable for the normal functioning of the neuroendocrine system. In this context, preliminary pharmacological evidence showed that histaminergic neuromodulation of the vasopressinergic system is mediated through H₁ receptors in the Ah, H₁ receptors in the ME and Nh, and both H₁ and H₂ receptors in the PFC and hypothalamus.

Stimulation of brain mast cells by compound 48/80, a histamine liberator, evokes renin and vasopressin release in dogs

“…In this study, not only a small dose of histamine, but also C48/80, evoked a significant increase in plasma ADH. It is well known that histamine given into the cerebral ventricle greatly elevates ADH secretion (2,7,15,57,63). When we administered 37.5 g/kg C48/80 into the V III , the increase in ADH from the basal level (2.6 times) was roughly equal to that in PRA (2.3 times).…”

“…Antidiuretic hormone (ADH), along with the renin-angiotensin system, is of great importance in regulating the defenses against both stress and cardiovascular dysfunction (57). The stress-induced increases in both renin secretion (5,14,29,30,33,44,55) and ADH (2,7,15,57) depend upon increases in the production of histamine and its receptors. Thus, these data seem to suggest that in the regulation of both renin and ADH secretion during stress reactions, histamine may act as a neurotransmitter within the hypothalamus (14,25,33,54,59).…”

Hippocampal somatostatin receptors and modulation of adenylyl cyclase activity in histamine-treated rats

“…Centrally administered SS produces a dose-related decrease in histamine levels in the rat hippocampus [7]. Ample evidence exists for histaminergic projections to the hippocampus [33,53], a brain area rich in SS content and receptors [21,40].…”

Time- and dose-dependent responses of brain histamine to intracerebroventricular and intraperitoneal administrations of growth hormone-releasing factor (GRF1-44).

“…Cacabelos et al 1984, 1985a, b ; Cacabelos et al 1985bCacabelos et al , 1987 or neuroregulator (Prell and Green 1986). HA cell bodies are located in the posterior region of the hypothalamus (Panula et al 1984 ; Steinbusch and Mulder 1984 ;Watanabe et al 1984 ;Senba et al 1985) sending axons in apparently organized ascending and descending pathways to the cortex (Takeda et al 1984) and spinal cord (Wahlestedt et al 1985).…”

“…Our previous neurochemical studies suggested that there are three main intrahypothalamic HA pathways from the posterior hypothalamus to the anterior hypothalamus, median eminence and neurohypophysis (Cacabelos 1984(Cacabelos , 1985bCacabelos et al 1985b), where abundant HA fibers are detected by immunohistochemical methods using antibodies against HA (Steinbusch and Mulder 1984) and histidine decarboxylase ; Senba et al 1985 ; Inagaki et al, unpublished data). These intrahypothalamic HA pathways are supposed to regulate neuroendocrine functions (Cacabelos 1984(Cacabelos , 1985a and particularly corticotropinergic (Cacabelos et al 1983Cacabelos 1984Cacabelos , 1985b) and vasopressinergic (Cacabelos 1984(Cacabelos , 1985bCacabelos et al 1987) systems. However, HA can also influence other neuroendocrine axes, as described in several reviews (Weiner and Ganong 1978;Roberts and Calcutt 1983;Cacabelos 1984Cacabelos ,1985a, b ; Donoso and Alvarez 1984; Tuomisto and Mannisto 1985).…”