Katsuyoshi Tojo

Inhibition by antiserum to Vasoactive Intestinal Polypeptide (VIP) of prolactin secretion induced by serotonin in the rat

Intraventricular (i.c.v.) injection of serotonin (5HT) or intravenous (i.v.) injection of 5-hydroxytryptophan (5HTP), a precursor of 5HT, raised plasma prolactin (PRL) levels in urethane-anesthetized rats pretreated with normal rabbit serum. When the animals were injected i.c.v. or i.v. with specific anti-VIP rabbit serum, the plasma PRL responses to 5HT and 5HTP were blunted. These findings suggest that hypothalamic VIP is involved, at least in part, in PRL secretion induced by central serotonergic stimulation in the rat.

Further evidence that peptide histidine isoleucine (PHI) may function as a prolactin releasing factor in rats

Intraventricular administration of peptide histidine isoleucine (PHI) (200 ng, 1, 5 and 10 micrograms/rat) resulted in a significant and dose-related increase in plasma prolactin (PRL) levels in urethane-anesthetized rats and in conscious rats with intraatrial and intraventricular catheters. Intravenous injection of PHI (10 micrograms/rat) also raised plasma PRL levels in these animals. In in vitro studies, PRL release from superfused rat anterior pituitary cells was stimulated by PHI (10(-9), 10(-8) and 10(-7) M) in a dose-related manner. The stimulating effect of PHI (10(-7)M) on PRL release in vitro was as potent as that of vasoactive intestinal polypeptide (VIP) (10(-7) M) and was observed even in the presence of dopamine (10(-7) M). These results suggest that PHI plays a stimulating role in regulating PRL secretion by acting, at least in part, directly on the pituitary in the rat.

Involvement of Hypothalamic Vasoactive Intestinal Polypeptide (VIP) in Prolactin Secretion Induced by Serotonin in Rats

Abstract To study the possible involvement of hypothalamic vasoactive intestinal polypeptide (VIP) in regulating the secretion of prolactin (PRL), the effect of anti-VIP rabbit serum on serotonin (5-HT)-induced PRL release was examined in urethane-anesthetized male rats. Anti-VIP serum (AVS) or normal rabbit serum (NRS) was infused into a single hypophysial portal vessel of the rat for 40 min at a rate of 2 μl/min with the aid of a fine glass cannula and 5-HT was injected into a lateral ventricle 10 min after the start of the infusion. Intraventricular injection of 5-HT (10 μg/rat) caused an increase in plasma PRL levels in control animals infused with NRS and 5-HT-induced PRL release was blunted in animals infused with AVS (mean±SE peak plasma PRL: 118.9±19.8 ng/ml vs 54.7±16.2 ng/ml, p<0.05). These findings suggest that the secretion of PRL induced by 5-HT is mediated, at least in part, by hypothalamic VIP release into the hypophysial portal blood in the rat.

Central effects of DN1417, a novel TRH analog, on plasma glucose and catecholamines in conscious rats

Intracerebroventricular (icv) injection of DN1417 (0.3, 3 and 30 nmol/rat), a TRH analog, resulted in a dose-related increase in plasma glucose, epinephrine and norepinephrine levels in conscious male rats. The effects of DN1417 were more potent and longer-lasting than those of TRH on a molar basis. Intravenous injection of DN1417 (30 nmol/rat) did not change plasma glucose, epinephrine and norepinephrine levels. Pretreatment with hexamethonium (1.5 mg/100 g body wt, iv, 2 min before) inhibited plasma glucose, epinephrine and norepinephrine responses to DN1417 (3 nmol/rat, icv). DN1417 did not change plasma glucose, epinephrine and norepinephrine levels in rats after total adrenalectomy. In the animals pretreated with cysteamine (30 mg/100 g body wt, sc, 4 h before), basal plasma glucose, epinephrine and norepinephrine levels were raised, and exaggerated responses of plasma glucose, epinephrine and norepinephrine to DN1417 (3 nmol/rat, icv) were obtained. These results indicate that DN1417 has a potent and long-lasting effect in the central nervous system in stimulating the secretion of catecholamines through the autonomic nervous system, which is associated with an elevation of plasma glucose and that endogenous hypothalamic somatostatin may inhibit the action of DN1417.

Inhibition by Antiserum to Rat Growth Hormone-Releasing Factor of Growth Hormone Secretion Induced by A Met5-Enkephalin Analog, FK33-824, in Rats

Abstract A Met5-enkephalin analog, FK33-824 (5, 10 and 20 ug/100 g body wt, iv) caused a dose-related increase in plasma growth hormone (GH) in urethane-anesthetized male rats. Pretreatmentwith cysteamine (30 mg/100 g body wt, sc), a depletor of hypothalamic somatostatin, increased the plasma GH response to FK33-824 (10 ug/100 g body wt, iv). Antiserum specific for rat GH-releasing factor (GRF)(0.5 ml/rat, iv) blunted GH release induced by FK33-824 (10 ug/100 g body wt, iv) in rats with or without cysteamine pretreatment. These results suggest that GH secretion induced by the opioid peptide is mediated, at least in part, by hypothalamic GRF in the rat.

Further Evidence that Central Neurotensin Inhibits Pituitary Prolactin Secretion by Stimulating Dopamine Release from the Hypothalamus

Abstract Intracerebroventricular (icv) injection of neurotensin (NT) (2 μg/rat) suppressed prolactin (PRL) release induced by L-5-hydroxytryptophan (1 mg/100 g body wt, iv), prostaglandin E2 (1 μg/rat, icv), and FK33-824 (10 μg/100 g body wt, iv), a Met5-enkephalin analog, in urethane-anesthetized or conscious rats. In contrast, NT did not suppress elevated plasma PRL levels sustained by a large dose of domperidone (10 μg/100 g body wt, iv), a peripheral dopamine antagonist. In in vitro experiments, NT (10-5 M) stimulated dopamine release from perifused rat hypothalamic fragments. These results suggest that central NT inhibits PRL secretion by stimulating dopamine release from the hypothalamus into hypophysical portal blood in the rat.

Stimulation by serotonin of immunoreactive peptide histidine isoleucine release from rat hypothalamus in vitro

The effect of serotonin (5-HT) on the release of peptide histidine isoleucine-like immunoreactivity (PHI-LI) from rat hypothalamus was investigated in vitro with a perifusion system. A high potassium concentration (56 mM) stimulated PHI-LI release in a calcium-dependent manner. PHI-LI release was dose-relatedly stimulated by 5-HT (10(-6), 10(-5) and 10(-4) M). PHI-LI release induced by 5-HT (10(-5) M) was abolished by cyproheptadine (10(-4) M), a 5-HT antagonist. These results suggest that 5-HT has a stimulating effect on PHI release from the hypothalamus.

Involvement of Peptide Histidine Isoleucine (PHI) In Prolactin Secretion Induced by Serotonin in Rats

Abstract The possible role of hypothalamic peptide histidine iso-leucine (PHI) in prolactin (PRL) secretion induced by serotoninergic mechanisms was investigated in male rats using a passive immunization technique. Intracerebroventricular injection of serotonin (5HT, 10 yg/rat) raised plasma PRL levels both in urethane-anesthetized rats and in conscious rats pretreated with normal rabbit serum (0.5 ml/ rat, iv, 30 min before). Plasma PRL responses to 5HT were blunted in these animals when they were pretreated with rabbit antiserum specific for PHI (0.5 ml/rat, iv, 30 min before)(mean±SE peak plasma PRL: anesthetized rats 271.3±38.3 ng/ml vs 150.0±12.6 ng/ml, p<0.01, conscious rats 54.3±6.8 ng/ml vs 30.7±4.1 ng/ml, p<0.025). These results suggest that hypothalamic PHI is involved, at least in part, in PRL secretion induced by central serotoninergic stimulation in the rat.