Histamine-Induced Prolactin Release: Pharmacological Characterization of Receptors in Male Rats

The possible involvement of the serotoninergic system in histamine-induced PRL secretion was studied in urethane anesthetized male rats. Intracerebroventricular infusion of histamine (30 µg) stimulated PRL secretion 10-fold. This effect was mimicked by the H₂-receptor agonist dimaprit (300 µg), while the H₁-receptor agonist 2-thiazolylethylamine (140 µg) had no effect. Pretreatment with the serotonin receptor blockers methysergide (2.5 mg/kg i.p.) or ketanserin (2.5 or 10.0 mg/kg i.p.) reduced the PRL peak response to histamine 75, 54, or 58%, respectively. During serotonin receptor blockade, dimaprit had a stimulatory effect similar to that of histamine, while 2-thiazolylethylamine had no effect. Intra-arterial infusion of histamine (420 µg) stimulated PRL secretion 6-fold. This effect was mimicked by the H₁-receptor agonist 2-thiazolylethylamine (1,900 µg), while the H₂-receptor agonist dimaprit (3,000 µg) had no effect. Pretreatment with methysergide (2.5 mg/kg i.p.) or ketanserin (2.5 or 10.0 mg/kg i.p.) reduced the peak response to histamine 54, 54, or 51%, respectively. The effect of histamine was mimicked by 2-thiazolylethylamine, while dimaprit slightly inhibited the PRL secretion. The antiserotoninergic activity of methysergide and ketanserin was demonstrated by their ability to prevent the PRL-releasing effect to serotonin. The effects of methysergide and ketanserin were not due to dopamine-like activity, since none of the drugs affected basal PRL secretion and since the dopamine receptor antagonist pimozide did not prevent the inhibitory effect of methysergide on the histamine-induced PRL release. The findings indicate that histamine-stimulated PRL secretion is mediated in part by serotoninergic neurons.

Section: Discussionsupporting

confidence: 85%

mentioning

confidence: 99%

Histaminergic Regulation of Prolactin Secretion: Involvement of Serotoninergic Neurons

Knigge

Sleimann²,

Matzen³

et al. 1988

“…Moreover, when these drugs were injected into the lateral ventricles of the brain they did not increase blood prolactin (PRL) levels [II]. These results together with the reported data that H2 antagonists centrally administered, exert inhibitory influ ence on PRL release induced by histamine [3,15] suggest that cimetidine, in addition to its specific H2 antagonistic action, may exert other pharmacological effects responsible for PRL enhancement. Recently data have been published that demonstrate that cimetidine is able to inhibit the bind ing of benzodiazepines and y-aminobutyric acid (GABA) to brain receptors [8,19], This led us to investigate whether or not the GABA-ergic system is involved in the stimulatory effect of cimetidine on PRL secretion.…”

mentioning

confidence: 87%

Cimetidine-Induced Prolactin Release: Possible Involvement of the GABA-Ergic System

Sibilia¹,

Netti²,

Guidobono³

et al. 1985

The mechanism of cimetidine-induced prolactin (PRL) release was studied. Intracarotid (i.a.) administration of 1 mg/kg of impromidine, the most specific H₂ histamine agonist known, did not counteract the cimetidine-induced hypersecretion of PRL. Pre-treatment with benzodiazepines (diazepam or lorazepam, 3 mg/kg/i.a.) completely suppressed it. Administration of γ-aminobutyric acid (GABA 5 mg/kg/i.a.) was also able to prevent it, but to a lesser extent than benzodiazepines. Simultaneous administration of doses of diazepam (1.5 mg/kg/i.a.) and GABA (3 mg/kg/i.a.) ineffective per se markedly blunted the increase of PRL by cimetidine. We conclude that cimetidine does not induce hypersecretion of PRL by its action on histamine H₂ receptors, but through other pharmacological activities of the drug, such as perhaps interaction with the GABA-ergic system in the pituitary.

“…It has previously been shown that histamine (HA) stimu lates prolactin (PRL) secretion dose dependently when in fused intracerebroventricularly or systemically (intra-arte rially) in male rats [8,15, 29] or in humans [17]. The stimu lation of PRL secretion following intracerebroventricular infusion of HA is mediated via Hi receptors, since the effect is blocked by Hi receptor antagonists and mimicked by H2 receptor agonists [8,15,16].…”

mentioning

confidence: 99%

“…The stimu lation of PRL secretion following intracerebroventricular infusion of HA is mediated via Hi receptors, since the effect is blocked by Hi receptor antagonists and mimicked by H2 receptor agonists [8,15,16]. In contrast, the stimulatory ef fect following intra-arterial infusion is mediated via Hi re-' Presented in part at the 14th Meeting of the European Hista mine Research Society, Aachen, FRG, May 1985, and at the 1st International Congress of Neuroendocrinology, San Francisco, Calif., USA, July 1986.…”

mentioning

confidence: 99%

Histaminergic Regulation of Prolactin Secretion: Involvement of Tuberoinfundibular Dopaminergic Neurons

Knigge

Matzen²,

Warberg³

1988

It has been shown that histamine (HA) stimulates prolactin (PRL) secretion via H₂ receptors following intra-cerebroventricular infusion and via Hi receptors following systemic (intra-arterial) infusion. Since the effect of HA appears to be exerted at a suprapituitary level, we investigated the involvement of the tuberoinfundibular dopaminergic (TIDA) system in HA-induced PRL secretion in urethane-anesthetized male rats. HA infused intracerebroventricularly (30 µg) or intra-arterially (420 µg) decreased the dopamine (DA) concentration in pituitary portal blood by 30 and 23%, respectively. Blockade of DA receptors by pimozide did not prevent the stimulation of PRL secretion induced by intracere-broventricular infusion of HA or the H₂ receptor agonist dimaprit. Furthermore, during DA receptor blockade intracere-broventricular infusion of the H₁ receptor agonist 2-thiazolylethylamine inhibited PRL secretion. In contrast, pimozide prevented the stimulation of PRL secretion induced by intra-arterial infusion of HA and the H₁ receptor agonist 2-thiazolylethylamine. In fact, under these conditions intra-arterial infusion of HA or the H₂-receptor agonist dimaprit inhibited PRL secretion. During treatment with α-methyl-p-tyrosine, which reduced the hypothalamic DA content by 50%, HA infused intracerebroventricularly stimulated PRL secretion, while HA infused intra-arterially inhibited the secretion, which is in accordance with the results obtained during pimozide treatment. Cholinergic blockade by atropine did not prevent the HA-induced PRL release, exluding the possibility that the observed effect of pimozide is due to its anticholinergic property. We suggest that intracerebroventricular infusion of HA by activation of H₂ receptors may stimulate PRL secretion partly via inhibition of the TIDA system and partly via other mechanisms. Furthermore, by activation of H₁ receptors, intracerebroventricularly infused HA seems to inhibit PRL secretion by a DA-independent mechanism. In contrast, intra-arterial infusion of HA may by activation of H₁ receptors stimulate PRL secretion preferentially via inhibition of the TIDA system, while the H₂ receptor mediated PRL-inhibiting effect of intra-arterially infused HA may be related to other mechanisms.