pituitrin and glucagon-like-peptide-1-(7-36)amide

Glucagon-like peptide-1 (7-36) amide (tGLP-1) has been shown to modify the secretory function of the rat hypothalamo-neurohypophysial complex (HNC). However, mechanisms underlying this action are still unclear. Using explants containing the HNC obtained from euhydrated rats, possible interactions of tGLP-1 with angiotensin II (Ang II), forskolin-induced cAMP synthesis or calcium ions were investigated. In addition, explants taken from rats given 2% saline were used in order to examine whether chronic osmotic stimulation affects tGLP-1 action on vasopressin and oxytocin neurons. tGLP-1 did not modify Ang II- or forskolin-evoked hormone release. Incubation of the HNC in calcium-free medium inhibited the tGLP-1-dependent vasopressin/oxytocin secretion. Prolonged salt loading in vivo completely changed the neurohypophysial response to tGLP-1 in vitro; it did not only abolish the stimulatory effect of tGLP-1 on basal hormone release, but reduced K(+)-stimulated vasopressin/oxytocin secretion. Consequently, the neurohypophysial response to tGLP-1 may depend on the functional status of the HNC and on the presence of calcium ions, but not cAMP.

Topics: Analysis of Variance; Angiotensin II; Animals; Calcium; Colforsin; Cyclic AMP; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Hypothalamo-Hypophyseal System; Male; Neurotransmitter Agents; Organ Culture Techniques; Oxytocin; Peptide Fragments; Rats; Rats, Wistar; Second Messenger Systems; Vasopressins; Water-Electrolyte Balance

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.

Topics: Animals; Blood Pressure; Dose-Response Relationship, Drug; Female; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Hypertension; Injections, Intravenous; Male; Neurotransmitter Agents; Oxytocin; Peptide Fragments; Radioimmunoassay; Rats; Rats, Wistar; Sex Factors; Time Factors; Vasopressins