Signaling cascades involved in neuroprotection by subpicomolar pituitary adenylate cyclase-activating polypeptide 38.

In neuronal/glial cocultures, pituitary adenylate cyclase-activating polypeptide 38 (PACAP38) prevented neuronal death induced by gp120, lipopolysaccharide (LPS), or other toxic agents, but the dose response of the neuroprotective effect is bimodal, with a peak at a subpicomolar concentration and another peak at a subnanomolar to nanomolar concentration. Although the signaling cascade involved in neuroprotection by nanomolar concentration of the peptide has been shown to be mediated by activation of cAMP-dependent protein kinase and subsequent activation of mitogen-activated protein kinase (MAPK), the mechanism for neuroprotection by a subpicomolar level of PACAP38 remains elusive. In the present study, the signaling involved in neuroprotection by subpicomolar PACAP38 was studied in rat neuronal/glial cocultures.

Salsolinol induces a decrease in cyclic AMP at the median eminence and an increase at the adenohypophysis in lactating rats.

Investigating the cellular events in the pituitary gland, the intracellular cyclic AMP (cAMP) of the median eminence (ME), neuro-intermediate lobe (NIL) and the anterior lobe (AL) have been measured following 15-min of intravenous injection of salsolinol (SAL). Parallel to the elevation of plasma prolactin (PRL), SAL induced a significant decrease of cAMP concentration in the ME. In contrast, SAL injection resulted in a significant increase of cAMP at the level of the AL.

Pituitary adenylate cyclase activating polypeptide: a potential neuroprotective peptide.

Pituitary adenylate cyclase activating polypeptide (PACAP) was first isolated from hypothalamic extracts on the basis of its ability to stimulate cAMP formation in pituitary cells. PACAP is widely distributed in the central and peripheral nervous systems and exerts numerous effects. Currently available data indicate that PACAP is a promising neuroprotective peptide.

Endomorphins exit the brain by a saturable efflux system at the basolateral surface of cerebral endothelial cells.

Endomorphin-1 (EM-1) and endomorphin-2 (EM-2) are two highly selective mu-opiate receptor agonists. We recently demonstrated that EM-1 and EM-2 have a saturable transport system from brain-to-blood in vivo. Since the endothelial cells are the main component of the non-fenestrated microvessels of the blood-brain barrier (BBB), we examined whether these endogenous tetrapeptides have a saturable transport system in cultured cerebral endothelial cells.

The effect of PACAP on rhythmic melatonin release of avian pineals.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a ubiquitous member of the VIP/secretin/glucagon bioactive peptide family. The distribution, concentration of PACAP, and its role in the control of rhythmic melatonin (MT) secretion from chicken pineal gland were studied. In the chicken pineal gland (ChPG), 40ng PACAP/g tissue was measured with radioimmunoassay.

Rapidly activated microglial cells in the preoptic area may play a role in the generation of hyperthermia following occlusion of the middle cerebral artery in the rat.

Postischemic hyperthermia occurs after the occlusion of the middle cerebral artery (MCAO) with an intraluminal filament in rats. The cause of hyperthermia is presumed to be damage to the preoptic area, which is one of the temperature-regulatory centers of the hypothalamus. In the present study, reactions of microglial cells and astrocytes in the preoptic area were examined during the first 6 h following transient MCAO.

PACAP inhibits anoxia-induced changes in physiological responses in horizontal cells in the turtle retina.

Pituitary adenylate cyclase activating polypeptide (PACAP) has neurotrophic and neuroprotective effects against various cytotoxic agents in vitro, and ischemia in vivo. Anoxia tolerance is most highly developed in some species of turtles. Recently, we have demonstrated high levels of PACAP38 in the turtle brain, exceeding those in corresponding rat and human brain areas by 10- to 100-fold.

Influence of pinealectomy on levels of PACAP and cAMP in the chicken brain.

One of the recently found functions of pituitary adenylate cyclase activating polypeptide (PACAP) is the modulation of circadian rhythms. Widespread distribution of PACAP-containing neurons and receptors has been shown in the chicken. Recently, we have demonstrated that PACAP levels oscillate in a circadian manner in the chicken brain.

Filament size influences temperature changes and brain damage following middle cerebral artery occlusion in rats.

Postischemic spontaneous hyperthermia as a complication of occlusion of the middle cerebral artery with an intraluminal filament has been observed by some authors, but many other reports do not discuss this factor. The possible reasons why some of the authors have not seen severe hyperthermia in their experiments include differences in surgical technique, the strain of animals, the type of the anesthesia, and the occluder filament. The aim of this study was to examine the changes in the core temperature of rats using different types of filaments.