Characterisation of Pea Milk Analogues Using Different Production Techniques.

Research background: Among legumes, peas are characterised by their high protein content, low glycaemic index and exceptional versatility. However, their potential as a food is often compromised by their undesirable off-flavour and taste. Hence, this study focuses on minimising off-flavours through simple pretreatments with the aim of improving the potential for the production of pea milk analogues. Pea milk analogues are a burgeoning type of plant-based milk alternatives in the growing plant-based market. Experimental approach: Pea seeds were subjected to different pretreatments: (i) dry milling, (ii) blanching followed by soaking in alkaline solution and subsequent dehulling and (iii) vacuum. Typical physicochemical properties such as pH, viscosity, colour, titratable acidity and yield were measured to obtain a brief overview of the products. Consumer acceptance test, descriptive sensory analysis, gas chromatography-mass spectrometry and gas chromatography-olfactometry were used to map the complete sensory profile and appeal of the pea milk substitutes. Results and conclusions: The L* values of the pea milk analogues were significantly lower than those of cow's milk, while a*, b*, viscosity and pH were similar. In the descriptive sensory analysis, sweet, astringent, pea-like, cooked, hay-like, boiled corn and green notes received relatively higher scores. The vacuum-treated pea milk analogues received higher scores for flavour and overall acceptability in the consumer acceptance test. The pretreatments resulted in significant changes in the volatile profiles of the pea milk analogues. Some volatiles typically associated with off-flavour, such as hexanal, were found in higher concentrations in blanched pea milk analogues. Among the applied pretreatments, vacuum proved to be the most effective method to reduce the content of volatile off-flavour compounds. Novelty and scientific contribution: This study stands out as a rare investigation to characterise pea milk analogues and to evaluate the impact of simple pretreatments on the improvement of their sensory properties. The results of this study could contribute to the development of milk alternatives that offer both high nutritional value and strong appeal to consumers.

The effect of different pre-treatments on unformulated pulse-based milk analogs: physicochemical properties and consumer acceptance.

This is the first part of a study on developing pulse-based milk analogs using chickpea, faba bean, and cowpea as raw materials. The objectives of the present study were to determine the processing conditions for pulse-based milk analog production at laboratory-scale and to investigate the effects of some pre-treatments such as dry milling (control), soaking and wet milling, blanching, blanching and dehulling, vacuum, and germination on lipoxygenase (LOX) activity of the raw material and some physicochemical and sensory properties of the final products. Dry milling provided the lowest LOX activity and the highest yield while soaking and wet milling resulted in a substantial increase in LOX activity, lower product yield, and a final product with lower whiteness value, regardless of the pulse type. Germination caused a significant decrease in LOX activity in all pulse types, while milk analogs produced from germinated pulses received the lowest acceptability scores from consumers. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05836-7.

Monitoring starch hydrolysis with micro visco-amylo-graph for the production of chickpea milk and optimization of the parameters with response surface methodology.

Plant-based milk products are gaining attention since it has been demonstrated that the consumption of animal-derived foods had to be reduced to combat global climate change. The production of plant-based milk includes a starch hydrolysis step for raw materials with high starch content such as cereals and pulses, since the gelatinized starch forms a thick slurry which causes an unsuitable consistency for a drinkable product. The objectives of this work were to investigate the effects of slurry concentration (solid to solvent ratio), enzyme including temperature, enzyme amount and mixing (rotation) speed on the pasting properties especially final viscosity of a crude chickpea milk and also to investigate the potential use of Micro Visco Amylo-Graph for monitoring starch hydrolysis. Response surface methodology, based on Box Behnken Design, was used to assess the parameters and to optimize the hydrolysis conditions for the minimum final viscosity. In conclusion, it was observed that slurry concentration and enzyme including temperature were the most critical factors that affect either the pasting properties or the final viscosity of the crude chickpea milk. Briefly, lower final viscosities were obtained from samples which were prepared at lower beginning concentrations and treated with higher enzyme amounts at lower temperatures.

Extrusion cooking of immature rice grain: under-utilized by-product of rice milling process.

Immature rice grain is one of the by-products of paddy milling process. Due to being "whole grain", immature rice grains comprise the fat-rich bran layer which bring along high nutritional value as well as susceptibility to rancidity. Therefore, they are generally used as "feed" rather than "food". In this study, the potential of utilizing immature rice grain as a food ingredient was investigated. For this purpose, raw (unprocessed) and infrared (IR) stabilized immature rice grain flours (IRGF) were extruded at different exit-die temperatures (130 °C and 150 °C) and feed moisture contents (16%, 18%, 20%) and the effects of these parameters on chemical composition (moisture, crude fat, protein, ash, soluble and insoluble dietary fiber and phytic acid contents), physicochemical properties (solubility, water binding capacity, expansion index and bulk density), thiamine, riboflavin and tocopherol contents, textural and sensorial properties of the extrudates were investigated. Either thiamine or tocopherol contents of the extrudates made of unprocessed IRGF were higher than that of the extrudates made of IR stabilized IRGF (p < 0.05). Additionally, higher extrusion temperature and lower feed moisture content resulted in further loss in both vitamins. On the other side, riboflavins showed a relatively heat-stable behavior. Rancid flavor and bitter taste scores of the extrudates which were made of unprocessed IRGF were significantly higher than their counterparts made of IR stabilized IRGF (p < 0.05). Toothpack was the most dominant sensory attribute in all extrudates.

Utilization of lentil, pea, and faba bean hulls in Turkish noodle production.

Turkish noodles (eriste) were substituted with green lentil (Lens culinaris), red lentil (L. culinaris), faba bean (Vicia faba), and pea (Pisum sativum) hulls at the level of 2.5, 5, and 10% and the effects of the substitution on proximate composition, mineral composition, colour, cooking properties, thiamine and riboflavin contents, texture and sensory properties of the noodles were investigated. Crude ash, dietary fibre, Ca and Mg contents of the noodles significantly increased with pulse hull substitution regardless of the hull type compared to control. Lightness or brightness (L*) values of the noodles showed a general decreasing trend with increasing pulse hull substitution excluding pea hull. L* value of the pea hull substituted noodles was higher than that of the control. Water absorption and swelling volume of the noodles remarkably increased with pea hull substitution. Thiamine and riboflavin contents of the control noodles and the noodles substituted with the noted hull types up to 10% were very close to each other. Noodles substituted with faba bean hull at the level of 10% showed the highest hardness, gumminess, and chewiness values. Pea hull substitution up to 10% did not significantly affected the sensory (appearance, texture and overall acceptability) scores of the panellists.

The effect of ultrasound on some properties of pulse hulls.

The aim of this study was to understand the effects of different ultrasound conditions on dietary fiber, phytic acid, total phenolics content, water and oil binding capacity, antioxidant capacity and phenolic acid composition of hull from green and red lentils (Lens culinaris), faba bean (Vicia faba), and pea (Pisum sativum). The highest and the lowest total dietary fiber content was observed in red lentil and faba bean hulls, respectively. Insoluble dietary fiber contents of the untreated pulse hulls were above 66% regardless of the pulse type. Phytic acid content of the pulse hulls ranged between 1.37 and 1.66 mg/g and was not affected from either the pulse type or ultrasound treatment. High and significant correlations were found between total phenolics content and Trolox equivalent antioxidant capacity both of which showed higher values for lentil hulls. Bound (hydrolyzable) extracts contained higher amounts of phenolic acids compared to free form extracts. Protocathechuic, p-coumaric and ferulic acids either in free or bound (hydrolyzable) form were present in hull from all the pulses. Ultrasound treated samples showed significantly lower total phenolic content and TEAC values compared to control for lentil hulls, while no consistent trend was observed for phenolic acids with regard to the ultrasound conditions.

Vasoactive Intestinal peptide modulates c-Fos activity in the trigeminal nucleus and dura mater mast cells in sympathectomized rats.

Neurogenic inflammation in the dura mater caused by trigeminal nociceptive activation has been implicated in the pathophysiology of migraine. Vasoactive intestinal polypeptide (VIP) is a powerful neuroprotective neuropeptide that can modulate mast cell behavior. Migraine is also associated with sympathetic insufficiency. This study investigates the effects of VIP on the number of mast cells in the dura mater and on c-Fos expression in the trigeminal nucleus of sympathectomized rats. Experiments were carried out with 32 Sprague-Dawley male rats with body weights of 200-250 g. In the sympathectomized group, the left superior cervical sympathetic ganglion was removed. In the sympathectomized + VIP group, postoperative VIP 25 ng/kg/day (0.2 ml) was administered for 5 days. In the sham group, the ganglion and nerves were exposed but not dissected. Dura maters were stained with toluidine blue, and brainstems were labeled by indirect immunohistochemistry for c-Fos. Sympathectomy significantly increased the number of mast cells in both the ipsilateral and the contralateral dura mater (P < 0.001). VIP decreased the number of mast cells in both sides of the dura mater in sympathectomized rats. VIP also decreased c-Fos expression in the ipsilateral trigeminal nucleus of sympathectomized rats (P < 0.001). In the context of an experimental superior cervical ganglionectomy model of migraine, VIP is an efficient modulator of neurogenic inflammation of the dura.

The impact of milling degree on physicochemical, nutritional, rheological, textural properties, and in vitro digestibility of rice: From brown rice to white rice.

The objective of this study was to characterize the rice milling fractions acquired at each stage of a commercial milling system. This characterization included an analysis of color, ash content, dietary fiber, mineral composition, as well as antinutritional compounds like phytic acid, trypsin inhibitor activity, and saponin. Additionally, we investigated in vitro starch and in vitro protein digestibility, along with pasting, cooking, and textural properties. Our findings revealed that milling improved the visual appeal of rice (e.g., volume expansion, weight gain, whiteness) and notably enhanced its starch digestibility. However, milling reduced dietary fiber, mineral content, antinutrients, cooking time, and texture characteristics such as hardness, chewiness, gumminess, springiness, and cohesiveness to varying degrees. Certain parameters, such as dietary fiber, exhibited a gradual change with the duration of milling, while others, such as mineral content and texture, showed significant variation at the initial stage of milling, particularly at the first mill.

The effects of bupivacaine injection and oral nitric oxide on extraocular muscle in the rabbit.

AIM: Nitric oxide (NO) plays a key role in muscle regeneration, which is the primary response, observed during bupivacaine-induced extraocular muscle (EOM) hypertrophy. Our aims were to investigate the effects of bupivacaine injection into the rabbit EOM and the interaction with NO. MATERIALS AND METHODS: Superior rectus (SR) muscles of 24 New Zealand albino rabbits were studied. Single muscle twitch tension (SMTT) and tetanic muscle tensions at 50, 75, and 100 Hz were recorded using a 15 V stimuli. The rabbits were equally allocated into three groups. Measurements were performed without any drug treatments in group 1. In groups 2 and 3, bupivacaine, 0.5 ml of a 0.50 % solution, was injected into the EOM, and after 21 days, measurements were performed. Oral isosorbide dinitrate (NO donor) at 20 mg/day was given each day prior to measurements in group 3. RESULTS: SMTTs were 69.9 (66.7-77.6), 187.7 (114.9-252.1) and 204.2 (135.3-311.6) mg in groups 1, 2, and 3 respectively. SMTTs for both groups 2 and 3 were significantly higher than that for group 1 (p < 0.05). Compared with group 1, group 2 exhibited a 3.8-11.7 % increase in the tetanic tensions at 50, 75, and 100 Hz, but none of these differences were statistically significant. The increase was 47.5-137.5 % in group 3 relative to group 2, and the differences were statistically significant except at 100 Hz. The enlargement of the muscle fibers after bupivacaine injection was shown histopathologically. CONCLUSION: Bupivacaine injection increased the EOM tension in rabbits to some extent. NO augmented the effect of bupivacaine.

Stabilization of Rice Bran: A Review.

One of the major problems in food science is meeting the demand of the world's growing population, despite environmental limitations such as climate change, water scarcity, land degradation, marine pollution, and desertification. Preventing food from going to waste and utilizing nutritive by-products as food rather than feed are easy and powerful strategies for overcoming this problem. Rice is an important staple food crop for more than half of the world's population and substantial quantities of rice bran emerge as the main by-product of rice grain milling. Usually, rice bran is used as animal feed or discarded as waste. Although it is highly nutritious and comprises many bioactive compounds with considerable health benefits, the rapid deterioration of bran limits the exploitation of the full potential of rice bran. Hydrolytic rancidity is the main obstacle to using rice bran as food, and the enzyme inactivation process, which is termed stabilization, is the only way to prevent it. This study reviews the methods of stabilizing rice bran and other rice-milling by-products comprising rice bran in the context of the efficiency of the process upon storage. The effect of the process on the components of rice bran is also discussed.

Vasoactive intestinal peptide (VIP) conducts the neuronal activity during absence seizures: GABA seems to be the main mediator of VIP.

Absence epilepsy is classified as a childhood generalized epilepsy syndrome with distinctive electroencephalographic patterns. The Wistar Albino Glaxo originating from Rijswijk (WAG/Rij) strain is a very well validated animal model of absence epilepsy that also shows behavioral deficits. In addition to the gastrointestinal system, VIP is highly expressed throughout numerous brain regions, and it plays crucial roles as a neurotransmitter and as a neuromodulatory, neurotrophic and neuroprotective factor in both the central and peripheral nervous systems. In this study, adult WAG/Rij rats were divided into two groups (n = 10): a group that was administered VIP (25 ng/kg i.p.) every 2 days for 15 days and an age-matched control group that was administered physiological saline. Electrical brain activity and behavior (depressive- like behavior, learning and memory and anxiety) were investigated in both groups. In addition, the extracellular concentrations of GABA and glutamate and the GABA/glutamate ratio were measured by high-performance liquid chromatography in microdialysate samples collected from the somatosensorial cortex of WAG/Rij rats. Our results demonstrated that VIP treatment significantly suppressed the total duration and number of spike wave discharges in WAG/Rij rats. However, VIP had no significant effect on behavior. VIP increased the extracellular concentration of GABA and the GABA/glutamate ratio in the somatosensory cortex. In conclusion, VIP has suppressive effects on absence seizures, possibly by increasing the GABA concentration and inducing the transformation of glutamate to GABA in the somatosensory cortex of WAG/Rij rats.

Vasoactive Intestinal Peptide Decreases ß-Amyloid Accumulation and Prevents Brain Atrophy in the 5xFAD Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by extracellular deposits of fibrillary ß-amyloid (Aß) plaques in the brain that initiate an inflammatory process resulting in neurodegeneration. The neuronal loss associated with AD results in gross atrophy of affected regions causing a progressive loss of cognitive ability and memory function, ultimately leading to dementia. Growing evidence suggests that vasoactive intestinal peptide (VIP) could be beneficial for various neurodegenerative diseases, including AD. The study investigated the effects of VIP on 5xFAD, a transgenic mouse model of AD. Toward this aim, we used 20 5xFAD mice in two groups (n = 10 each), VIP-treated (25 ng/kg i.p. injection, three times per week) and saline-treated (the drug's vehicle) following the same administration regimen. Treatment started at 1 month of age and ended 2 months later. After 2 months of treatment, the mice were euthanized, their brains dissected out, and immunohistochemically stained for Aß40 and Aß42 on serial sections. Then, plaque analysis and stereological morphometric analysis were performed in different brain regions. Chronic VIP administration in 5xFAD mice significantly decreased the levels of Aß40 and Aß42 plaques in the subiculum compared to the saline treated 5xFAD mice. VIP treatment also significantly decreased Aß40 and Aß42 plaques in cortical areas and significantly increased the hippocampus/cerebrum and corpus callosum/cerebrum ratio but not the cerebral cortex/cerebrum ratio. In summary, we found that chronic administration of VIP significantly decreased Aß plaques and preserved against atrophy for related brain regions in 5xFAD AD mice.

Advantages of Vasoactive Intestinal Peptide for the Future Treatment of Parkinson's Disease.

Parkinson's disease is the second most common neurodegenerative disorder in adults over the age of 65. The characteristic symptoms of Parkinson's disease, such as resting tremor, muscular rigidity, bradykinesia, postural instability and gait imbalance, are thought to be a result of the progressive degeneration of the dopaminergic neurons of the substantia nigra compacta, resulting in insufficient dopamine integrated signalling on GABAergic medium spiny neurons in the striatum. Despite tremendous research, the molecular mechanisms underlying the pathogenesis of neurodegeneration in Parkinson's disease have remained largely unknown. Although a variety of possible pathogenic mechanisms have been proposed over the years, including excessive release of oxygen free radicals, impairment of mitochondrial function, loss of trophic support, abnormal kinase activity, disruption of calcium homeostasis, dysfunction of protein degradation and neuroinflammation, the pathogenesis is still largely uncertain, and there is currently no effective cure for Parkinson's disease. To develop potential therapies for Parkinson's disease, inflammatory processes, mitochondrial dynamics, oxidative stress, production of reactive aldehydes, excitotoxicity and synucleinopathies are to be targeted. In this respect, vasoactive intestinal peptide has beneficial effects that provide an advantage for the treatment of Parkinson's disease. Vasoactive intestinal peptide is a major neuropeptide-neurotransmitter having antioxidant, anti-inflammatory, neurotropic, neuromodulator, and anti-apoptotic properties. In addition to its direct neuroprotective actions regulating the activity of astrocytes, microglia and brain mast cells, it also plays important roles for neuronal adaptation, maintenance and survival.

Stabilization of immature rice grain using infrared radiation.

Immature rice grain is one of the underutilized by-products of paddy milling process. Despite its high potential of use as a food ingredient, it is mainly utilized as feed due to the rancidity problem. In the present study, the composition of immature rice grain, the potential of using infrared (IR) radiation for stabilization, and the effects of IR stabilization on color, fatty acid composition, tocopherol and γ-oryzanol contents of the grain were investigated. The free fatty acid (FFA) value of the unprocessed immature rice grain was 5.49% and increased to 35.71% at the end of 3 months of storage at room temperature. However, FFA content of the grains stabilized with IR radiation at specific conditions remained unchanged throughout the storage period. Moreover, IR stabilization did not caused a negative effect on the noted components of the immature rice grain.

Vasoactive intestinal peptide, a promising agent for myopia?

AIM: To investigate the role of vasoactive intestinal peptide (VIP) in form-deprivation myopia (FDM). METHODS: FDM was created in three groups of eight chicks by placing a translucent diffuser on their right eyes. Intravitreal injections of saline and VIP were applied once a day into the occluded eyes of groups 2 and 3, respectively. Retinoscopy and axial length (AL) measurements were performed on the first and 8th days of diffuser wear. The retina mRNA levels of the VIP receptors and the ZENK protein in right eyes of the three groups and left eyes of the first group on day 8 were determined using real time polymerase chain reaction (PCR). RESULTS: The median final refraction (D) in right eyes were -13.75 (-16.00, -12.00), -11.50 (-12.50, -7.50), and -1.50 (-4.75, -0.75) in groups 1, 2, and 3, respectively (P<0.001). The median AL (mm) in right eyes were 10.65 (10.00, 11.10), 9.90 (9.70, 10.00), and 9.20 (9.15, 9.25) in groups 1, 2, and 3, respectively (P<0.001). The median delta-delta cycle threshold (CT) values for the VIP2 receptors were 1.07 (0.82, 1.43), 1.22 (0.98, 1.65), 0.29 (0.22, 0.45) in right eyes of groups 1, 2, and 3, and 1.18 (0.90, 1.37) in left eyes of group 1, respectively (P=0.001). The median delta-delta CT values for the ZENK protein were 1.07 (0.63, 5.03), 3.55 (2.20, 5.55), undetectable in right eyes of groups 1, 2, and 3 and 1.89 (0.21, 4.73) in left eyes of group 1, respectively (P=0.001). CONCLUSION: VIP has potential inhibitory effects in the development of FDM.

Effect of vasoactive intestinal peptide on the wound healing of alkali-burned corneas.

AIM: To study the effect of vasoactive intestinal peptide (VIP) on wound healing in experimental alkali burns of the cornea. METHODS: Twenty-seven albino rabbits, weighing 3.2±0.75 kg were used. Alkali burns were induced on corneas by applying 10 mm Whatman paper No:50 soaked in 1 mol/L NaOH. They have further classified into 5 groups as follows: 1) control group given no treatment (n=5); 2) VIP given subconjunctivally (n=6); 3) VIP injected into anterior chamber (n=6); 4) NaCl 0.9% given subconjunctivally (n=5); 5) NaCl 0.9% given into the anterior chamber (n=5). All treatment protocols except control group were followed by topical eye drops composed of VIP at two hourly intervals for one week from 8 a.m. to 6 p.m. RESULTS: VIP treated groups of rabbits with alkali burns were found to have better wound healing findings histo-pathologically when compared to those of control group who have received no treatment on day 30. No differences were observed between groups in respect to degree of polymorphonuclear leukocytes (PMNL) infiltration and degree of loss of amorphous substrate on day 15. However, PMNL infiltration and degree of loss of amorphous substrate were lower in Groups 2 and 3 when compared to that of control group on day 30 (P<0.05). CONCLUSION: We have shown that VIP has positive effects on alkali induced corneal burns. VIP may inhibit PMNL migration to cornea through an immunomodulatory effect. Inhibition of PMNL migration might reduce the release of collagenases and this might prevent the extracellular amorphous substance loss.

Modulation of Corpus Striatal Neurochemistry by Astrocytes and Vasoactive Intestinal Peptide (VIP) in Parkinsonian Rats.

The neurotoxin 6-hydroxydopamine (6-OHDA) is widely used in animal models of Parkinson's disease. In various neurodegenerative diseases, astrocytes play direct, active, and critical roles in mediating neuronal survival and functions. Vasoactive intestinal peptide (VIP) has neurotrophic actions and modulates a number of astrocytic activities. In this study, the effects of VIP on the striatal neurochemistry were investigated in parkinsonian rats. Adult Sprague-Dawley rats were divided into sham-operated, unilaterally 6-OHDA-lesioned, and lesioned + VIP-administered (25 ng/kg i.p.) groups. VIP was first injected 1 h after the intrastriatal 6-OHDA microinjection and then every 2 days throughout 15 days. Extracellular striatal concentration of glutathione (GSH), gamma-aminobutyric acid (GABA), glutamate (GLU), and lactate were measured in microdialysates by high-performance liquid chromatography (HPLC). Quantification of GABA and activity dependent neuroprotective protein (ADNP)-expressing cells were determined by glutamic acid decarboxylase (GAD)/ADNP + glial fibrillary acidic protein (GFAP) double immunohistochemistry. Our results demonstrated that a 6-OHDA lesion significantly increased the density of astrocytes in the striatum and VIP treatment slightly reduced the gliosis. Extracellular concentration of GABA, GLU, and lactate levels did not change, but GSH level significantly increased in the striatum of parkinsonian rats. VIP treatment reduced GSH level comparable to sham-operated groups, but enhanced GABA and GLU levels. Our double labeling results showed that VIP primarily acts on neurons to increase ADNP and GAD expression for protection. These results suggest that, in the 6-OHDA-induced neurodegeneration model, astrocytes were possibly activated for forefront defensiveness by modulating striatal neurochemistry.

Brain mast cells and therapeutic potential of vasoactive intestinal peptide in a Parkinson's disease model in rats: brain microdialysis, behavior, and microscopy.

In the present study, the effect of systemically administered vasoactive intestinal peptide (VIP) (25 ng/kg i.p.) was investigated on drug-induced rotational behavior, extra-cellular dopamine levels and histology of corpus striatum in a 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinson's disease. After 15 days of 6-OHDA lesion, apomorphine-induced (0.05 mg/kg s.c.) rotational behavior of the animals significantly increased and extra-cellular dopamine levels of corpus striatum were significantly reduced. VIP reversed the rotational deficits but did not alter the decrease in striatal dopamine levels. On the other hand, histological data indicate that VIP significantly reduced neuronal death and demyelination. Electron microscopic appearance of mast cells showed ultra-structural variety between VIP-treated and 6-OHDA lesioned groups. VIP activates mast cells without any evidence of typical exocytosis, and possibly mast cells could participate in neuroprotection. Our results suggest that systemically administered VIP can attenuate the motor response changes, neuronal cell death, and myelin sheet loss characteristically associated with 12 microg 6-OHDA administration into the rat striatum. Brain mast cells seem to participate in neuronal protection. Possibly, protective cues could be produced by brain mast cells.

Passage of VIP/PACAP/secretin family across the blood-brain barrier: therapeutic effects.

In recent years, VIP/PACAP/secretin family has special interest. Family members are vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), secretin, glucagon, glucagon like peptide-1 (GLP(1)), GLP(2), gastric inhibitory peptide (GIP), growth hormone releasing hormone (GHRH or GRF), and peptide histidine methionine (PHM). Most of the family members present both in central nervous system (CNS) and in various peripheral tissues. The family members that are released into blood from periphery, especially gut, circulate the brain and they can cross the blood brain barrier. On the other hand, some of the members of this family that present in the brain, can cross from brain to blood and reach the peripheral targets. VIP, secretin, GLP(1), and PACAP 27 are transported into the brain by transmembrane diffusion, a non-saturable mechanism. However, uptake of PACAP 38 into the brain is saturable mechanism. While there is no report for the passage of GIP, GLP(2), and PHM, there is only one report that shows, glucagon and GHRH can cross the BBB. The passage of VIP/PACAP/secretin family members opens up new horizon for understanding of CNS effects of peripherally administrated peptides. There is much hope that those peptides may prove to be useful in the treatment of serious neurological diseases such as Alzheimer's disease, amyotropic lateral sclerosis, Parkinson's disease, AIDS related neuropathy, diabetic neuropathy, autism, stroke and nerve injury. Their benefits in various pathophysiologic conditions undoubtly motivate the development of a novel drug design for future therapeutics.

Passage of vasoactive intestinal peptide across the blood-brain barrier.

We investigated the ability of vasoactive intestinal peptide (VIP) to cross the blood-brain barrier (BBB), the interface between the peripheral circulation and central nervous system (CNS). VIP labeled with 131I (I-VIP) and injected intravenously into mice was taken up by brain as determined by multiple-time regression analysis. Excess unlabeled VIP was unable to impede the entry of I-VIP, indicating that passage is by nonsaturable transmembrane diffusion. High pressure liquid chromatography (HPLC) showed the radioactivity entering the brain to be intact I-VIP. After intracerebroventricular (i.c.v.) injection, I-VIP was sequestered by brain, slowing its efflux from the CNS. In summary, VIP crosses the BBB unidirectionally from blood to brain by transmembrane diffusion.