Biomedical subjects

Jolanta B Zawilska

Publications and source records attributed to Jolanta B Zawilska.

At least 19 recordsLinked to original sources

PubMed2006

Daily oscillation in melatonin synthesis in the Turkey pineal gland and retina: diurnal and circadian rhythms.

The aim of the present study was to examine arylalkylamine N-acetyltransferase (AANAT) activity and melatonin content in the pineal gland and retina as well as the melatonin concentration in plasma of the turkey (Meleagris gallopavo), an avian species in which several physiological processes, including reproduction, are controlled by day length. In order to investigate whether the analyzed parameters display diurnal or circadian rhythmicity, we measured these variables in tissues isolated at regular time intervals from birds kept either under a regular light-dark (LD) cycle or under constant darkness (DD). The pineal gland and retina of the turkey rhythmically produced melatonin. In birds kept under a daily LD cycle, melatonin levels in the pineal gland and retina were high during the dark phase and low during the light phase. Rhythmic oscillations in melatonin, with high night-time concentrations, were also found in the plasma. The pineal and retinal melatonin rhythms mirrored oscillations in the activity of AANAT, the penultimate enzyme in the melatonin biosynthetic pathway. Rhythmic oscillations in AANAT activity in the turkey pineal gland and retina were circadian in nature, as they persisted under conditions of constant darkness (DD). Transferring birds from LD into DD, however, resulted in a potent decline in the amplitude of the AANAT rhythm from the first day of DD. On the sixth day of DD, pineal AANAT activity was still markedly higher during the subjective dark than during the subjective light phase; whereas, AANAT activity in the retina did not exhibit significant oscillations. The results indicate that melatonin rhythmicity in the turkey pineal gland and retina is regulated both by light and the endogenous circadian clock. The findings suggest that environmental light may be of primary importance in the maintenance of the high-amplitude melatonin rhythms in the turkey.

Animals↗

PubMed2005

Diurnal and circadian rhythms in melatonin synthesis in the turkey pineal gland and retina.

The pineal gland and retina of the turkey rhythmically produce melatonin. In birds kept under a daily light-dark (LD) illumination cycle melatonin concentrations in the pineal gland and retina were low during the light phase and high during the dark phase. A similar melatonin rhythm with high night-time values was also observed in the plasma. The pineal and retinal melatonin rhythms mirror oscillations in the activity of serotonin N-acetyltransferase (AANAT; the penultimate enzyme in the melatonin biosynthetic pathway). In contrast, in both the pineal gland and retina the activity of the enzyme hydroxyindole-O-methyltransferase (HIOMT) did not exhibit significant changes throughout the 24-h period. Acute exposure of turkeys to light at night dramatically decreased melatonin levels in the pineal gland, retina and plasma. The rhythms in AANAT activity and melatonin concentrations in the turkey pineal gland and retina were circadian in nature as they persisted under conditions of constant darkness (DD). Under DD, however, the amplitudes of AANAT and melatonin rhythms were significantly lower (by 50-80%) than those found under the LD cycle. The findings indicate that melatonin rhythmicity in the turkey pineal gland and retina is regulated both by light and the endogenous circadian clock. The rapid dampening of the rhythms under DD suggests that of these two regulatory factors, environmental light may be the primary stimulus in the maintenance of the high amplitude melatonin rhythms in the turkey.

Acetylserotonin O-Methyltransferase↗

PubMed2005

Near-ultraviolet light perceived by the retina generates the signal suppressing melatonin synthesis in the chick pineal gland-an involvement of NMDA glutamate receptors.

Exposure of dark-adapted chicks to near ultraviolet (UV-A) light significantly decreased melatonin (MEL) content and the activity of serotonin N-acetyltransferase (AA-NAT; the penultimate and key regulatory enzyme in MEL production) in the pineal glands. Significant reduction in MEL level and AA-NAT activity was also found in pineals of animals whose heads were covered with black opaque tape, an observation suggesting that in the chicken UV-A light perceived by the eyes alone is capable of affecting MEL synthesis in the pineal gland. Covering the chick's eyes, in addition to the head, totally blocked the studied UV-A action. Although SCH 23390 (a selective D1-dopamine receptor antagonist), injected directly into both eyes at a dose of 10 nmol/eye, prevented the decline in pineal AA-NAT activity produced by retinal illumination with white light, the drug did not modify the UV-A light-evoked decrease in the enzyme activity. MK-801 (a selective antagonist of NMDA glutamate receptors; 1 nmol/eye) abolished the suppressive action of UV-A light on pineal AA-NAT activity, but it was inactive in the case of white light. Intraocularly injected sulpiride and CNQX (selective antagonists of D2-dopamine and AMPA/kainite glutamate receptors, respectively) had no effect on the actions of both UV-A and white light (acting on the eyes only) on pineal AA-NAT activity. It is concluded that in the chick retinally perceived UV-A light generates a signal which suppresses MEL production in the pineal gland. At the level of the retina, such signal does not involve dopamine, but is dependent on the stimulation of NMDA glutamate receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2005

Posthatching developmental changes in noradrenaline content in the chicken pineal gland.

Noradrenaline (NA) levels in pineal gland of chickens at various posthatching stages (P2, P4, P8, P15, P30 and P57) were determined by high-performance liquid chromatography with electrochemical detection. Pineal NA content markedly increased between P2 and P30. P30 and P57 chickens, kept from the day of hatching under a 12:12 hr light-dark (LD) illumination cycle, exhibited rhythmic changes in pineal NA, with levels in the dark period being markedly higher than in the light period. In younger birds pineal NA concentrations did not show pronounced daily variations. In 4-wk-old chickens (P28-30) kept under constant darkness (DD), the rhythmic pattern of pineal NA persisted for 1 day (with higher values during the subjective dark phase than during the subjective light phase), but this disappeared 24 hr after the introduction of DD. In contrast, NA content in pineal glands isolated from birds maintained for 2 days under continuous light was similar to that found during the light phase of the LD cycle, and did not exhibit significant rhythmicity. In P30 chickens, pretreated with alpha-methyl-p-tyrosine (AMPT, an inhibitor of tyrosine hydroxylase, the key regulatory enzyme in the biosynthesis of catecholamines), pineal NA content declined slowly and monophasically during the light phase. During the dark phase the AMPT-induced decay of NA was biphasic--namely an initial rapid decline over the first 15 min which was followed by a slow-rate decline--an observation indicating that NA turnover was higher in the dark. Acute exposure of the dark-adapted P30 and P57 chickens to light significantly decreased pineal NA content, but did not affect pineal NA concentrations in younger birds. Our results suggest that the NA rhythm in the chicken pineal gland and its sensitivity to light regulation progressively develop during the first month of life.

Aging↗

PubMed2005

UV-A light regulation of arylalkylamine N-acetyltransferase activity in the chick pineal gland: role of cAMP and proteasomal proteolysis.

Acute exposure of dark-adapted, cultured chick pineal glands to UV-A light significantly decreased the tissue cAMP concentration and the activity of arylalkylamine N-acetyltransferase (AANAT), the penultimate and key regulatory enzyme in the melatonin biosynthetic pathway. The magnitude of these changes was dependent on the duration of UV-A exposure. The UV-A light-evoked decline in pineal AANAT activity was blocked by cAMP protagonists (forskolin and dibutyryl-cAMP) and by inhibitors of the proteasomal degradation pathway (MG-132, proteasome inhibitor I, and lactacystin). These results indicate that the chick pineal gland is directly sensitive to UV-A light. By analogy to white light, the suppressive action of UV-A radiation on AANAT activity in the chick pineal gland involves changes in the tissue cAMP level and enhanced proteasomal proteolysis.

Acetylcysteine↗

PubMed2005

Receptors for VIP and PACAP in guinea pig cerebral cortex: effects on cyclic AMP synthesis and characterization by 125I-VIP binding.

Receptors for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) in guinea pig cerebral cortex were characterized by (1) radioreceptor binding of 125I-labeled VIP (human/rat/porcine), and (2) cyclic AMP (cAMP) formation. Saturation analysis of 125I-VIP binding to membranes of guinea pig cerebral cortex resulted in a linear Scatchard plot, suggesting the presence of a single class of high-affinity receptor-binding sites, with a Kd of 0.63 nM and a B(max) of 77 fmol/mg protein. Various peptides from the PACAP/VIP/secretin family displaced the specific binding of 125I-VIP to guinea pig cerebrum with the relative rank order of potency: chicken VIP (cVIP) > or = PACAP38 approximately PACAP27 approximately guinea pig VIP (gpVIP) > or = mammalian (human/rat/porcine) VIP (mVIP) > peptide histidine-methionine (PHM) > peptide histidine-isoleucine (PHI) > secretin. Analysis of the competition curves revealed displacement of 125I-VIP from high- and lower-affinity binding sites, with IC50 values in the picomolar and the nanomolar range, respectively. About 70% of the specific 125I-VIP-binding sites in guinea pig cerebral cortex were sensitive to Gpp(NH)p, a nonhydrolyzable analog of GTP. Pituitary adenylate cyclase-activating polypeptide 38 (PACAP38), PACAP27, cVIP, gpVIP, mVIP, PHM, and PHI stimulated cAMP production in [3H]adenine-prelabeled slices of guinea pig cerebral cortex in a concentration-dependent manner. Of the tested peptides, the most effective were PACAP38 and PACAP27, which at a 1 microM concentration produced a 17- to 19-fold rise in cAMP synthesis, increasing the nucleotide production to approx 11% conversion above the control value. The three forms of VIP (cVIP, mVIP, and gpVIP) at the highest concentration used, i.e., 3 microM, produced net increases in cAMP production in the range of 8-9% conversion, whereas 5 microM PHM and PHI, by, respectively, 6.7% and 4.9% conversion. It is concluded that cerebral cortex of guinea pig contains VPAC- type receptors positively linked to cAMP formation. In addition, the observed stronger action of PACAP (both PACAP38 and PACAP27), when compared to any form of VIP, on cAMP production in this tissue, suggests its interaction with both PAC1 and VPAC receptors.

Amino Acid Sequence↗

PubMed2004

Retinal illumination phase shifts the circadian rhythm of serotonin N-acetyltransferase activity in the chicken pineal gland.

The pineal gland of birds, in contrast to its mammalian counterpart, is a directly photosensitive organ. It has recently been demonstrated that light also acting via the retina acutely suppresses melatonin synthesis in the chicken pineal gland. The present study was aimed to investigate whether retinal illumination alone was capable of resetting the biological oscillator generating the circadian rhythm of pineal serotonin N-acetyltransferase (AA-NAT) activity in the chicken. Ocular exposure of chickens to 6 h low intensity white light (4 lux) potently suppressed AA-NAT activity (the penultimate and key regulatory enzyme in the melatonin biosynthetic pathway) in the pineal gland. In addition, this light pulse produced phase-dependent shifts in the circadian AA-NAT rhythm. Exposure to light early in the subjective night (circadian time (CT) 12-18) caused a phase delay in the circadian rhythm of pineal AA-NAT activity by 3.5+/-0.4 h compared to non-exposed controls. When the light pulse was applied during the second half of the subjective night (CT18-24), it produced a large phase advance of the circadian rhythm of pineal AA-NAT activity by 10.9+/-0.4 h. The advancing effect of light was more pronounced than the phase-delaying effect. Our results suggest that in the chicken retinally perceived light provides a powerful and important signal for synchronization of circadian rhythmicity in the pineal gland.

Adaptation, Biological↗

PubMed2004

Receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide in turkey cerebral cortex: characterization by [125I]-VIP binding and effects on cyclic AMP synthesis.

Receptors for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) in turkey cerebral cortex were characterized using two approaches: (1) in vitro radioreceptor binding of [125I]-VIP, and (2) effects of peptides from the PACAP/VIP/secretin family on cyclic AMP formation. The binding of [125I]-VIP to turkey cortical membranes was rapid, stable, and reversible. Saturation analysis resulted in a linear Scatchard plot, suggesting binding to a single class of high affinity receptor binding sites with a Kd of 0.70 nM and a Bmax of 52 fmol/mg protein. Various peptides displaced the specific binding of 0.12 nM [125I]-VIP to turkey cerebral cortical membranes in a concentration-dependent manner. The relative rank order of potency of the tested peptides to inhibit [125I]-VIP binding to turkey cerebrum was: PACAP38 approximately PACAP27 approximately chicken VIP approximately mammalian VIP >>> PHI >> secretin, chicken VIP16-28 (inactive). About 65% of specific [125I]-VIP binding sites in turkey cerebral cortex was sensitive to Gpp(NH)p, a nonhydrolysable analogue of GTP. PACAP38, PACAP27, chicken VIP and, to a lesser extent, mammalian VIP potently stimulated cyclic AMP formation in turkey cerebral cortical slices in a concentration-dependent manner, displaying EC50 values of 8.7 nM (PACAP38), 21.3 nM (PACAP27), 67.4 nM (chicken VIP), and 202 nM (mammalian VIP). On the other hand, PHI and secretin very weakly affected the nucleotide production. The obtained results indicate that cerebral cortex of turkey contains VPAC type receptors that are positively linked to cyclic AMP-generating system and are labeled with [125I]-VIP.

Animals↗

PubMed2004

Suppression of melatonin biosynthesis in the chicken pineal gland by retinally perceived light - involvement of D1-dopamine receptors.

In this study the role of retinal dopamine (DA) receptors in the light-induced suppression of melatonin biosynthesis in the chicken pineal gland was examined. Exposure of dark-adapted chickens to low intensity light (4 lux) at night significantly decreased the activity of serotonin N-acetyltransferase (AA-NAT; the penultimate and key regulatory enzyme in melatonin production) and melatonin content in the pineal gland. This suppressive action of light was blocked by intraocular (i.oc.) administration of SCH 23390 (a selective antagonist of D1-DA receptors), but was not affected by sulpiride (a selective antagonist of D2-DA receptors). Injection of DA (i.oc.) to dark-adapted chickens significantly decreased pineal AA-NAT activity and melatonin content in a dose- and time-dependent manner. The action of DA was mimicked by selective agonists of D1-DA receptors, SKF 38393 and SKF 81297, and non-hydrolyzable analogs of cyclic AMP (cAMP), dibutyryl-cAMP and 8-bromo-cAMP. However, i.oc. administration of quinpirole, a selective agonist of D2-DA receptors, did not modify pineal AA-NAT activity. In contrast, quinpirole potently decreased nocturnal AA-NAT activity in the retina. Systemic administration of SCH 23390 to chickens blocked the i.oc. DA-evoked decline in nighttime pineal AA-NAT activity, whereas sulpiride was ineffective. These findings indicate that light activation of retinal dopaminergic neurotransmission, with concomitant stimulation of D1-DA receptors positively coupled to the cAMP generating system, plays an important role in a cascade of events regulating pineal activity.

Animals↗

PubMed2003

The relationship between melatonin and dopamine rhythms in the duck retina.

In the retina of duck, levels of dopamine (DA) and its main metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), fluctuate throughout the day, with high values during the light phase. The rhythmic changes in DA content and metabolism are out of phase with the daily oscillations in melatonin (MEL) and serotonin N-acetyltransferase (AA-NAT; the penultimate and key regulatory enzyme in MEL biosynthesis) activity. Acute exposure of ducks to light at night potently increased levels of DA and DOPAC, and decreased AA-NAT activity and MEL content in the retina. Intraocular administration of MEL to light-adapted ducks produced a significant decline in retinal DA and DOPAC concentrations. On the other hand, quinpirole, a D(2)/D(4)-DA receptor agonist, administered intraocularly, markedly suppressed the night-time retinal AA-NAT activity and MEL. These findings provide, for the first time, evidence for an inverse relationship between the DA system and MEL in the duck retina.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2003

PAC1 receptors in chick cerebral cortex: characterization by binding of pituitary adenylate cyclase-activating polypeptide, [125I]-PACAP27.

In this study we characterized receptors for pituitary adenylate cyclase-activating polypeptide (PACAP) in chick cerebral cortex by in vitro binding technique, using [125I]-PACAP27 as a ligand. The specific binding of [125I]-PACAP27 to chick cerebral cortical membranes was found to be rapid, stable, saturable, and of high affinity. Scatchard analysis suggested binding to a single class of receptor binding sites with high affinity (K(d)=0.41+/-0.08 nM) and high capacity (B(max)=457+/-35 fmol/mg protein). The relative rank order of potency of the tested peptides to inhibit [125I]-PACAP27 binding to chick cerebrum was: PACAP38 approximately PACAP27>PACAP6-27 approximately PACAP6-38 >> chicken VIP >> mammalian VIP >> secretin (inactive). It is concluded that the cerebral cortex of chick, in addition to VPAC recognition sites, contains a large population of PAC(1)-type receptor binding sites.

Animals↗

PubMed2003

Daily variation in the concentration of melatonin and 5-methoxytryptophol in the goose pineal gland, retina, and plasma.

The goose pineal gland rhythmically produces two 5-methoxyindole compounds, namely melatonin and 5-methoxytryptophol. Melatonin concentrations were high at night and low during the day, while in contrast 5-methoxytryptophol levels were markedly higher during the day compared to the night-time values. Rhythmic oscillations in melatonin content, with high night-time values, have also been found in plasma and the retina of goose. The pineal and retinal melatonin rhythm mirrored oscillations in the activity of serotonin N-acetyltransferase (AA-NAT; the penultimate and key regulatory enzyme in the melatonin biosynthetic pathway). Acute exposure of geese to light at night markedly decreased melatonin levels in the pineal, plasma, and retina. In addition, this light exposure resulted in a significant increase in pineal 5-methoxytryptophol content. Our results demonstrate, for the first time, the ability of the goose pineal gland and retina to synthesise melatonin and 5-methoxytryptophol in a rhythmic manner.

Animals↗

PubMed2003

Rhythmic changes in metabolism of dopamine in the chick retina: the importance of light versus biological clock.

Rhythmic changes in dopamine (DA) content and metabolism were studied in retinas of chicks that were adapted to three different lighting conditions: 12-h light : 12-h dark (LD), constant darkness (DD) and continuous light (LL). Retinas of chicks kept under LD conditions exhibited light-dark-dependent variations in the steady-state level of DA and the two metabolites of DA, i.e. 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA). Concentrations of DA, DOPAC and HVA were high in light hours and low in dark hours of the LD illumination cycle. In retinas of chicks kept under DD, the content of DA, DOPAC and HVA oscillated in a rhythmic manner for 2 days, with higher values during the subjective light phase than during the subjective dark phase. The amplitudes of the observed oscillations markedly and progressively declined compared with the amplitudes recorded under the LD cycle. In retinas of chicks kept under LL conditions, levels of DA, DOPAC and HVA were similar to those found during the light phase of the LD cycle. Changes in the retinal contents of DA and HVA did not exhibit pronounced daily oscillations, while on the first day of LL the retinal concentrations of DOPAC were significantly higher during the subjective light phase than during the subjective dark phase. Acute exposure of chicks to light during the dark phase of the LD cycle markedly increased DA and DOPAC content in the retina. In contrast, light deprivation during the day decreased the retinal concentrations of DA and DOPAC. It is suggested that of the two regulatory factors controlling the level and metabolism of DA in the retina of chick, i.e. light and biological clock, environmental lighting conditions seem to be of major importance, with light conveying a stimulatory signal for the retinal dopaminergic cells.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2003

Characterization of vasoactive intestinal peptide/pituitary adenylate cyclase-activating polypeptide receptors in chick cerebral cortex.

In this study receptors for vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) were characterized in chick cerebral cortex by an in vitro binding technique, using 125I-labeled VIP ([125I]-VIP) as a ligand. The specific binding of [125I]-VIP to chick cerebral cortical membranes was found to be rapid, stable, saturable, reversible, and of high affinity. Saturation analysis resulted in a linear Scatchard plot, suggesting binding to a single class of receptor binding sites with high affinity (Kd = 0.21 nM) and low capacity (Bmax = 19.5 fmol/mg protein). The relative rank order of potency of the tested peptides to inhibit [125I]-VIP binding to chick cerebrum was VIP (chicken) > or = VIP (mammalian) > or = PACAP27 > or = PACAP38 >> VIP6-28 (mammalian) > PHI (porcine) >> neurotensin6-11-chicken VIP7-28 > neurotensin6-11-mammalian VIP7-28 >>> VIP16-28 (chicken; inactive) approximately secretin (inactive). About 60% of [125I]-VIP-binding sites in chick cerebral cortex were sensitive to Gpp(NH)p, a nonhydrolyzable analog of GTP. It has been concluded that the cerebral cortex of chick, in addition to PAC1 receptors, contains a population of VPAC-type receptors.

Animals↗

PubMed2003

Antagonism of VIP-stimulated cyclic AMP formation in chick brain.

Of eight peptides tested (0.01-5 microM), only two, that is, pituitary adenylate cyclase-activating polypeptide (PACAP27) and chicken vasoactive intestinal peptide (cVIP), potently stimulated cyclic AMP (cAMP) production in cerebral cortical slices of the chick. Mammalian VIP (mVIP) showed some activity only at the highest dose tested, whereas truncated forms of PACAP or VIP, that is, PACAP6-27, cVIP6-28, and mVIP6-28, or hybrid compounds, that is, neurotensin6-11-cVIP7-28 (NT-cVIP) and neurotensin6-11-mVIP7-28 (NT-mVIP), were inactive. Thirty-minute preincubation of chick cortical slices with 5 microM PACAP6-27, NT-cVIP, or NT-mVIP competitively antagonized the cAMP effects of cVIP (0.03-1 microM), with the truncated form of PACAP being the best antagonist. Preincubation of slices with 5 microM mVIP6-28 also produced a significant inhibition of the cVIP (0.1-1 microM)-induced increase in cAMP production; however its action was independent of the concentration of cVIP. In contrast to mVIP6-28, cVIP6-28 showed no antagonistic activity against the full-length peptide. In parallel experiments, 30-min pretreatment of cortical slices with 5 microM PACAP6-27 significantly antagonized the PACAP38-evoked increase in cAMP formation, whereas mVIP6-28 or the NT-mVIP hybrid was ineffective. It has been concluded that in the chick brain, PACAP and cVIP stimulate cAMP biosynthesis via PAC1 and VPAC-type receptors, respectively, and PACAP6-27 seems to be the most potent, yet PACAP/VIP receptor-nonselective antagonist. Unlike truncated PACAP, the NT-VIP hybrid peptides tested may represent VPACtype receptor-selective blocking activity.

Animals↗

PubMed2003

PACAP in avians: origin, occurrence, and receptors--pharmacological and functional considerations.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a novel member of the secretin/glucagon/vasoactive intestinal peptide (VIP) superfamily. In vertebrates, including avians, it occurs in two forms: PACAP(38) and PACAP(27). PACAP structure is well conserved during evolution, being identical in mammals, and showing one amino acid dfifference in avians (chick, turkey). PACAP is widely distributed in the central nervous system and peripheral tissues and displays a pleiotropic activity, including functions as a hypophysiotropic hormone, neuromodulator, and neurotrophic factor. PACAP exerts its biological actions through three types of receptors designated PAC(1), VPAC(1) and VPAC(1). This review (1) presents the current knowledge on PACAP origin, distribution and function, (2) compares the avian findings with those found in mammals, and (3) describes receptor-linked mechanisms in avians, including recent data on receptor-related signal transduction pathways, with a special emphasis on receptor pharmacology and function.

Amino Acid Sequence↗

PubMed2003

[Dopamine receptors--structure, characterization and function].

Dopamine (DA) is an important neurotransmitter/neuromodulator that plays various functions within the body. In the central nervous system, DA is involved in the control of locomotion, cognition, emotion, neuroendocrine secretion and function of retinal cells. In the periphery, DA participates in the regulation of homeostasis, vascular tone and hormone secretion. The diverse physiological functions of DA are mediated by at least five distinct membrane bound receptors, i.e. D1 and D5--members of D1 family, and D2, D3, D4--members of D2 family of DA receptors. All DA receptors belong to the superfamily of G-protein-coupled receptors. This survey summarizes current knowledge on the molecular and pharmacological characterization of DA receptors, their role in the regulation of various processes in an organism, and involvement in the therapy of several disorders, in particular in the treatment of Parkinson's disease, schizophrenia, and hypertension.

Animals↗

PubMed2002

Stimulatory effects of pituitary adenylate cyclase-activating polypeptide on inositol phosphates accumulation in avian cerebral cortex and hypothalamus.

This study has demonstrated that the short and long form of the pituitary adenylate cyclase-activating polypeptide (PACAP), i.e. PACAP(27) and PACAP(38), moderately but significantly, and in a concentration (0.5-5 microM)-dependent manner, stimulated inositol phosphates (IPs) accumulation in myo-[(3)H]inositol-prelabeled cerebral cortical and hypothalamal slices of chick and duck, and in slices of rat cerebral cortex; both peptides had no effect on IPs formation in rat hypothalamus. Vasoactive intestinal peptide (VIP; 0.5-5 microM) weakly enhanced IPs accumulation in chick hypothalamus, had no significant action in chick cerebral cortex (in fact there was a tendency to attenuate the IPs response in this tissue), and slightly, but significantly, inhibited the IPs accumulation in rat cerebral cortex. VIP showed no activity in rat hypothalamus. It is concluded that the stimulatory action of PACAP on phosphoinositide metabolism in avian cerebral cortex, similar to rat cerebral cortex, is mediated via phospholipase C-linked PAC(1) type receptors. In chick hypothalamus, however, there may be a component of VPAC type receptors stimulating IPs formation.

Animals↗