Bozena Stempniak

Effects of centrally or systemically injected glucagon-like peptide-1 (7–36) amide on release of neurohypophysial hormones and blood pressure in the rat

The present study was designed to compare the effects of glucagon-like peptide-1 (7-36) amide (GLP-1) injected centrally or systemically in a dose range of 10-10000 ng on the vasopressin and oxytocin release as well as the blood pressure in the rat. The urethane-anaesthetised Wistar male and female rats were fitted with venous as well as arterial catheters and, in the second study, additionally with the intracerebroventricular cannula. The arterial blood pressure was monitored throughout the experiment. The plasma vasopressin/oxytocin concentrations were measured in blood samples taken 15 min before and 5, 15 and 30 min after the intravenous or intracerebroventricular GLP-1 injection. No gender-dependent differences were seen as to the GLP-1 effect on the blood pressure or the hormone release. GLP-1 administered centrally or systemically at low doses (10 or 100 ng) either showed a hypertensive or biphasic (an increase followed by a decrease in the blood pressure) effect. On the other hand, 1000 or 10000 ng GLP-1 caused a clear increase of the blood pressure regarding the way of injection. When injected systemically, GLP-1 increased the release of both neurohypophysial hormones. When injected centrally, however, GLP-1 either enhanced or, at low doses, significantly reduced the plasma vasopressin/oxytocin levels. The effect on the blood pressure seems to be independent of the possible pressor effect of endogenous vasopressin. It is concluded that GLP-1 may modulate the function of the hypothalamo-neurohypophysial system as well as the cardiovascular system through both the central and systemic mechanisms.

Melatonin, pinealectomy, and release of neurohypophysial hormones : in vitro studies

Abstract: The effect of melatonin as well as pinealectomy on the basal and K+‐evoked release of vasopressin and oxytocin from the neurointermediate lobes in vitro was determined. Pineal removal resulted in a diminution of vasopressin and oxytocin release from the neurointermediate lobes in vitro. Melatonin (10−3 or 10−6 M/1) increased vasopressin and oxytocin release from neurointermediate lobes of sham‐operated rats. Nevertheless, when pinealectomized rats served as donors of the neurointermediate lobes, melatonin (10−3 or 10−6 M/1) increased vasopressin release under basal conditions. For the same tissue, melatonin did not affect the oxytocin release either under basal conditions or during depolarization due to excess potassium. When 10−7 M/l melatonin was used, no changes in either vasopressin or oxytocin release were observed in vitro.

The effect of melatonin on suckling-induced oxytocin and prolactin release in the rat.

There is growing evidence that melatonin (MEL) inhibits oxytocin (OT) release when used in a low dose, while higher doses stimulate the release of the hormone in the rat. In the present study we investigated the effect of exogenous MEL, administered intracerebroventricularly (ICV), on suckling-induced OT and prolactin (PRL) release in the urethane-anesthetized rat. Lactating rats suckled by 8-12 pups were studied on days 8-12 of postpartum, and lactating pups-deprived rats on the same days of postpartum served as a control. Plasma OT and PRL levels as well as hypothalamic and neurohypophyseal OT contents were measured by RIA. Suckling stimulated the secretion of both OT and PRL. The ICV injection of 1 ng/ml MEL produced a significant inhibition of suckling-induced OT as well as PRL secretion. Melatonin in doses of 100 ng/ml or 10 micrograms/ml did not modify the OT release but significantly inhibited PRL release brought about by suckling; 10 pg/ml of MEL was not effective in this regard. Thus, exogenous MEL seems to inhibit suckling-induced OT as well as PRL secretion when applied at doses regarded to be in the range of the physiological level; when applied in higher doses, it was shown not to influence the release of OT following physiological stimulation such as suckling.

Melatonin inhibits the substance P-induced secretion of vasopressin and oxytocin from the rat hypothalamo-neurohypophysial system: In vitro studies

The aim of the present investigations was to study the influence of substance P (a member of a family of peptides known as tachykinins) on basal and K(+)-evoked vasopressin (AVP) and oxytocin (OT) release from rat hypothalamo-neurohypophysial system in vitro as well as to determine whether this effect of substance P is sensitive to melatonin. The present results show that substance P stimulates basal AVP and OT release from isolated hypothalamo-neurohypophysial system, when used at the concentrations of 10(-6) and 10(-7)M/l. At the concentration of 10(-9)M/l, however, substance P was found to stimulate the in vitro secretion of AVP, but not that of OT. Melatonin diminished basal release of AVP; it also significantly inhibited the substance P-stimulated secretion of AVP and OT. K(+)-evoked release of the neurohypophysial hormones was not further modified by either substance P or melatonin. The present results show that the stimulatory effect of substance P on basal release of AVP and OT from rat hypothalamo-neurohypophysial system in vitro is sensitive to inhibitory influence of melatonin.

Neurohypophyseal vasopressin in the Syrian hamster: response to short photoperiod, pinealectomy, melatonin treatment, or osmotic stimulation.

In the present study, the effect of photoperiod on vasopressin content in the pituitary neurointermediate lobe (NIL), as well as the ability of pinealectomy to prevent and melatonin to mimic the short photoperiod-induced changes in NIL vasopressin were studied in male Syrian hamsters. The ability of melatonin to modify the hyperosmotically stimulated vasopressin release was also determined. Exposure to short photoperiod (SD) for 4 or 10 weeks increased vasopressin content in the hamster NIL. In long photoperiod (LD)-exposed hamsters, pinealectomy induced a decrease in NIL vasopressin content, whereas no effect of melatonin injections on vasopressin storage in the NIL was detected. In SD-exposed animals, pineal removal failed to alter vasopressin content in the NIL. Hypertonic saline administration led to the expected decrease in vasopressin content in the NIL both in vehicle- and melatonin-treated animals. The hyperosmotically stimulated release of vasopressin was not modified by previous treatment with melatonin. The data from the present study show that, in male Syrian hamsters, exposure of animals to SD increases the vasopressin content in the posterior pituitary, but these changes appear not to be mediated by SD-induced changes in melatonin secretion. Furthermore, the exposure of animals to SD prevents the pinealectomy-induced changes in NIL vasopressin content. Melatonin does not modify the hyperosmotically stimulated vasopressin release in the male Syrian hamster.

Melatonin inhibits oxytocin and vasopressin release from the neurointermediate lobe of the hamster pituitary

THE aim of this investigation was to study whether melatonin affects the release of oxytocin and vasopressin by the pituitary neurointermediate lobe of the Syrian hamster in vitro. The effect of melatonin was studied on the unstimulated (pre- and post-K+-stimulated) release of oxytocin and vasopressin and on the response to K+stimulation. Melatonin significantly inhibited unstimulated release of these hormones in all concentrations (10-11 M, 10-9M and 10-7M) studied. K+-stimulated release of oxytocin and vasopressin was significantly decreased by the 10-9M dose of melatonin. It is concluded that melatonin is active in modifying the release of these peptides in the Syrian hamster neurointermediate lobe, as it has been previously demonstrated in the rat hypothalamus.

Neurohypophysial response to haemorrhage or dehydration: interactions of vasopressin and luliberin

Abstract Rats, euhydrated, dehydrated for two days or haemorrhaged, were given intracerebroventricularly (i.c.v.) luteinizing hormone releasing hormone (LH-RH) in a daily dose of 100 ng dissolved in 10 μl of 0.9% sodium chloride. In euhydrated rats, a single dose of LH-RH as well as the daily i.c.v. treatment with LH-RH over two days did not significantly affect either the plasma vasopressin concentrations or hypothalamo-neurohypophysial vasopressin content. On haemorrhage (1 ml per 100 g), the increase in plasma vasopressin was almost inhibited and the depletion of neurohypophysial hormone content significantly diminished in animals previously treated with LH-RH. Similarly, LH-RH attenuated markedly the enhanced vasopressin release from the hypothalamo-neurohypophysial system brought about by two-day dehydration. We suggest that LH-RH may have a regulatory role in the hypothalamo-neurohypophysial system especially under conditions of haemorrhage or hyperosmotic dehydration.

Thyroliberin and the daily rhythm of vasopressin and oxytocin release from the hypothalamo-neurohypophysial system

Abstract The daily rhythm of neurohypophysial hormones release was investigated in rats given intracerebroventricularly (i.c.v.) thyroliberin (200 ng/10 μ l—once daily over 4 days). In animals injected i.c.v. with vehicle solution (0.15 M sodium chloride) plasma vasopressin concentration was seen to rise over the hours of daylight, decreasing during the first part of the night; plasma oxytocin was the lowest in the morning and increased somewhat at midnight. The content of neurohypophysial vasopressin and oxytocin were highest in the morning; during the light hours they decreased progressively to minimum values at 18:00–19:00. Hypothalamic vasopressin content reached the maximum value at the midnight but hypothalamic oxytocin content was highest in the morning. Manifold injections of thyroliberin to rats resulted in a distinct decrease of neurohypophysial vasopressin and oxytocin content at the beginning of the day (06:00–07:00). Maximal values for neurohypophysial vasopressin at midday and also during the first phase of the night were observed; the same for oxytocin in the middle of the dark period was noted. The high increase of vasopressin and oxytocin plasma levels at the beginning of the day has been observed; the minimum for both vasopressin and oxytocin plasma concentrations during the dark period (24:00–01:00) has been observed. In the hypothalamus, thyroliberin impaired the basic rhythm of vasopressin as well as oxytocin release over the light hours and intensified distinctly this process during the night hours (i.e. a decrease of hypothalamic neurohormones content during the light period and its increase over the night hours). It is supposed that thyroliberin may considerably influence the rhythm of the vasopressin and oxytocin release from the hypothalamo-neurorohypophysial system.

tGLP-1 action on the isolated hypothalamo-neurohypophysial system under glutamate receptor blockade.

The isolated rat hypothalamo-neurohypophysial system was used to investigate possible mechanisms of glucagon-like peptide-1 (7-36) amide (tGLP-1) effects on the vasopressin/oxytocin (AVP/OXY) release. The non-selective inhibition of synaptic transmission as brought about by excess of MgSO(4) in the incubation medium completely abolished the tGLP-1-induced AVP release and attenuated OXY secretion. The non-specific blockade of excitatory amino acid receptors with kynurenic acid (KA) completely suppressed the tGLP-1-induced AVP but not OXY release. Specific inhibition of NMDA receptors suppressed the tGLP-1-evoked AVP release without affecting tGLP-1-induced OXY secretion. Selective blockade of non-NMDA receptors did not affect either tGLP-1-induced AVP or OXY release. It is concluded that tGLP-1 can influence the function of AVP neurons indirectly, most probably via the glutamatergic system through NMDA receptors. On the other hand, tGLP-1-evoked activation of OXY neurons, at least in part, seems to be a result of direct tGLP-1 activation of these neurons.

Effects of tGLP-1 on feeding behaviour and neurohypophysial function under chronic osmotic stimulation.

Effects of repeated daily intracerebroventricular injections of 1 microg of glucagon-like peptide-1 (7-36) amide (tGLP-1) on feeding and drinking behaviour, as well as neurohypophysial hormone secretion, was investigated in rats drinking tap water or 2% saline for 6 days. In euhydrated rats, tGLP-1 decreased moderately food and water consumption without a marked reduction of body weight. In salt-loaded rats, tGLP-1 considerably inhibited saline intake. On the other hand, food consumption and body weight changes were similar in vehicle- and tGLP-1-treated rats drinking 2% saline. Osmotic stimulation resulted in the augmented release of both neurohypophysial hormones. tGLP-1 did not alter plasma vasopressin and oxytocin concentrations either in euhydrated or osmotically stimulated rats. It is concluded that tGLP-1 may modify feeding and drinking behaviour under conditions of normal or disturbed water-electrolyte balance in the rat.