Dual effects of vasoactive intestinal peptide (VIP) on leucocyte migration

Vasoactive intestinal peptide, at different concentrations, was tested on the migration of leucocytes by using the sealed capillary migration test. Vasoactive intestinal peptide, at 10(-7)-10(-9)M, inhibited, while at 10(-12)-10(-14)M, stimulated mononuclear leucocyte migration. The migration of polymorphonuclear leucocytes was inhibited by vasoactive intestinal peptide at 10(-6)-10(-9)M, a stimulation was found at 10(-13)-10(-14)M. The inhibiting effect of vasoactive intestinal peptide on leucocyte migration was abolished when vasoactive intestinal peptide was split into C- and N-terminal fragments, while a stimulating effect was retained in the N-terminal fragment, at 10(-14)M, for mononuclear cells. Helodermin and peptide T, as well as two other members of the secretin-glucagon family, secretin and gastric inhibitory peptide, had no effect on the migration. When VIP antiserum was tested, it had an inhibiting effect, which was not seen with control serum, supporting a physiological effect of the lower vasoactive intestinal peptide concentrations. Vasoactive intestinal peptide seems to have dual effects on mononuclear and polymorphonuclear leucocyte migration and, generally, intact vasoactive intestinal peptide seems to be needed for these effects.     

Expression of histamine and vasoactive intestinal peptide (VIP) receptors in immortalized rat fetal intestinal cells

Four intestinal cell lines derived from rat fetuses at 19 days of gestation were successfully propagated after electroporation in the presence of different recombinant DNAs containing the viral oncogenes E1A from Adenovirus 5 and large T from SV40 or Polyoma. These immortalized intestinal cells, designated SLC, possess several properties observed in the parent cells of this tissue, including the expression of cytoplasmic villin, enkephalinase and retention of VIP receptors. In contrast, histamine elevated cAMP levels in the SLC cell lines only. the data suggest that the transfection of fetal rat intestinal cells by E1A and large T is associated with the induction of functional histamine receptors coupled with the Gs/Gi regulatory proteins of adenylate cyclase.     

Neither vasoactive intestinal peptide (VIP) nor purine derivatives may mediate non-adrenergic tracheal inhibition

Neurogenic responses in isolated electrical field stimulated guinea-pig tracheas include a prominent relaxation that is only partially inhibited by propranolol. The possibility that either purine derivatives or VIP could be a non-adrenergic inhibitory neurotransmitter was examined. Relaxant characteristics of adenosine, ATP, adenine and VIP in tracheas with different degrees of contraction were compared to those of maximal non-adrenergic nerve stimulation. Spontaneous tone and carbachol (5.5 microM and 55 microM)-contracted tracheas were inhibited 77.5 +/- 5.0% (n = 9), 24.7 +/- 2.8% (n = 11) and 14.5 +/- 5.0% (n = 10), respectively, by electrical nerve stimulation. At the three states of contraction exogenous VIP, but not adenosine, ATP, or adenine, produced relaxations similar to those of electrical nerve stimulation. In carbachol-contracted tracheas with maximally effective concentrations present of adenosine (3 mM), adenine (3 mM) or VIP (23.3 microM), the non-adrenergic neurogenic inhibitory response remained intact. The neurogenic inhibitory response was also unaffected by the presence of theophylline and indomethacin which blocked relaxatory effects of adenosine and ATP, respectively. The results suggests that neither the purine derivatives, nor VIP are involved in the non-adrenergic, neurogenic inhibition in the guinea-pig trachea.     

Depression of lymphocyte traffic in sheep by vasoactive intestinal peptide (VIP).

Vasoactive intestinal peptide (VIP) is a 28 amino acid-residue neurovascular and gut peptide with a number of important biological activities. Recent in vitro studies suggest an immunomodulatory (depressant) role for VIP. In the present in vivo studies, employing the Hall and Morris sheep lymphocyte traffic model, acute infusions of VIP into cannulated afferent lymphatics of popliteal lymph nodes produced prompt and marked depressions in the output of both small recirculating and blast lymphocytes into popliteal efferent lymph, with a selective effect on T4 (CD4) lymphocytes. It has been suggested that the HIV (AIDS) virus may employ VIP or VIP-like receptors on brain cells and lymphocytes for intracellular access.     

The significance of vasoactive intestinal polypeptide (VIP) in immunomodulation

Evidence for VIP influences on immune function comes from studies demonstrating VIP-ir nerves in lymphoid organs in intimate anatomical association with elements of the immune system, the presence of high-affinity receptors for VIP, and functional studies where VIP influences a variety of immune responses. Anatomical studies that examine the relationship between VIP-containing nerves and subpopulations of immune effector cells provide evidence for potential target cells. Additionally, the presence of VIP in cells of the immune system that also possess VIP receptors implies an autocrine function for VIP. The functional significance of VIP effects on the immune system lies in its ability to help coordinate a complex array of cellular and subcellular events, including events that occur in lymphoid compartments, and in musculature and intramural blood circulation. Clearly, from the work described in this chapter, the modulatory role of VIP in immune regulation is not well understood. The pathways through which VIP can exert an immunoregulatory role are complex and highly sensitive to physiological conditions, emphasizing the importance of in vivo studies. Intracellular events following activation of VIP receptors also are not well elucidated. There is additional evidence to suggest that some of the effects of VIP on cells of the immune system are not mediated through binding of VIP to its receptor.Despite our lack of knowledge regarding VIP immune regulation, the evidence is overwhelming that VIP can interact directly with lymphocytes and accessory cells, resulting in most cases, but not always in cAMP generation within these cells, and a subsequent cascade of intracellular events that alter effector cell function. VIP appears to modulate maturation of specific populations of effector cells, T cell recognition, antibody production, and homing capabilities. These effects of VIP are tissue-specific and are probably dependent on the resident cell populations within the lymphoid tissue and the surrounding microenvironment. Different microenvironments within the same lymphoid tissue may influence the modulatory role of VIP also. Effects of VIP on immune function may result from indirect effects on secretory cells, endothelial cells, and smooth muscle cells in blood vessels, ducts, and respiratory airways. Influences of VIP on immune function also may vary depending on the presence of other signal molecules, such that VIP alone will have no effect on a target cell by itself, but may greatly potentiate or inhibit the effects of other hormones, transmitters, or cytokines. The activational state of target cells may influence VIP receptor expression in these cells, and therefore, may determine whether VIP can influence target cell activity.Several reports described in this chapter also indicate that VIP contained in neural compartments is involved in the pathophysiology of several disease states in the gut and lung. Release of inflammatory mediators by cells of the immune system may destroy VIP-containing nerves in inflammatory bowel disease and in asthma. Loss of VIPergic nerves in these disease states appears to further exacerbate the inflammatory response. These studies indicate that altered VIP concentration can have significant consequences in terms of health and disease. In addition, the protective effects of VIP from tissue damage associated with inflammatory processes described in the lung also may be applicable to other pathological conditions such as rheumatoid arthritis, anaphylaxis, and the swelling and edema seen in the brain following head trauma. While VIP degrades rapidly, synthetic VIP-like drugs may be developed that interact with VIP receptors and have similar protective effects. Synthetic VIP-like agents also may be useful in treating neuroendocrine disorders associated with dysregulation of the hypothalamic—pituitary—adrenal axis, and pituitary release of prolactin.     

Effect of apamin on release of vasoactive intestinal polypeptide (VIP) from the cat intestines

The effect of apamin, a polypeptide from bee venom, on the release of vasoactive intestinal polypeptide (VIP) during active neurogenic vasodilatation in the intestines was studied in vivo in anesthetized cats. Three non-adrenergic, non-cholinergic mechanisms were investigated, i.e. the vasodilatation seen upon transmural electrical field stimulation, pelvic nerve activation and stimulation of the intramural nerves with 5-hydroxytryptamine (5-HT) infused i.a. Apamin given close i.a. abolished the three vasodilator responses. Concomitantly, the increase of VIP release was also markedly diminished although apamin increased the rate of VIP release seen in the "resting" control period. The results are in agreement with the hypothesis that VIP is the neurotransmitter in the three investigated vasodilator mechanisms.     

Comparison of vasoactive intestinal peptide (VIP) and secretin in gastric secretion and mucosal blood flow

Summary VIP and secretin were compared in regard to their effects on gastric acid and pepsin secretion induced by pentagastrin histamine or a peptone meal as well as on gastric mucosal blood flow and meal induced serum gastrin level in conscious dogs provided with gastric fistulas and denervated fundic pouches. Both VIP and secretin caused a dose-related stimulation of basal pepsin outputs and inhibition of pentagastrin-induced acid secretion. VIP, like secretin, inhibited pentagastrin and meal-induced gastric acid secretion but in contrast to secretin it caused inhibition of acid response to histamine. Inhibition of acid secretion by VIP or secretin was accompanied by secondary reduction in gastric mucosal blood flow in tests with pentagastrin or histamine and by depression of the serum gastrin level in tests with a peptone meal. This study indicates that in comparison with secretin, VIP has a wider spectrum of inhibition of stimulated gastric secretion and may be considered as one of the enterogastrones released in the small intestine.     

Release of immunoreactive vasoactive intestinal peptide (VIP) from the gallbladder in response to vagal stimulation

Immunoreactive VIP was detected in the gallbladder lumen and in the arterial blood and venous effluent from the gallbladder in fasting cats. During perfusion of the gallbladder in vivo there was a constant basal intraluminal secretion of VIP. The VIP concentration in the luminal effluent exceeded that in plasma supporting the notion that there was a release from the gallbladder tissue. The rate of secretion was significantly increased during efferent electrical stimulation of the peripheral cut end of the cervical vagal nerves, after blockade with atropine. A similar increase in concentration of VIP was seen in the venous effluent from the gallbladder. The results suggest a local release of VIP from intrinsic neurons within the gallbladder wall. This release is increased in response to activation of non-cholinergic fibres in the vagus nerves, suggesting a role for VIP in regulation of gallbladder functions.     

Regulation of inhibitory synaptic transmission by vasoactive intestinal peptide (VIP) in the mouse suprachiasmatic nucleus

Circadian rhythmicity in mammals is generated by a pair of nuclei in the anterior hypothalamus known as the suprachiasmatic nuclei (SCN), whose neurons express a variety of neuropeptides that are thought to play an important role in the circadian timing system. To evaluate the influence of VIP on inhibitory synaptic transmission between SCN neurons, we used whole cell patch-clamp recording in an acute brain slice preparation of mouse SCN. Baseline spontaneous GABAergic inhibitory postsynaptic currents (IPSCs) varied significantly between regions and across phases, with a greater frequency of IPSCs observed in the dorsomedial region during the early night. Bath-applied VIP caused a significant increase in the frequency of spontaneous inhibitory postsynaptic currents (sIPSC) in a reversible and dose-dependent manner with no effect on the mean amplitude or kinetic parameters. The effect of VIP was widespread throughout the SCN and observed in both ventrolateral (VL) and dorsomedial (DM) regions. In the presence of tetrodotoxin, VIP increased the frequency of miniature IPSCs without affecting the mean magnitude or kinetic parameters. The magnitude of the enhancement by VIP was significantly larger during the day than during the night. Pretreatment with the VIP-PACAP receptor antagonist [Ac-Tyr1, D-Phe2]-GHRF 1-29 or the selective VPAC2 receptor antagonist PG 99-465 completely blocked the VIP-induced enhancement. The effect of VIP appears to be mediated by a cAMP/PKA-dependent mechanism as forskolin mimics, while the PKA antagonist H-89 blocks the observed enhancement of GABA currents. Our data suggest that VIP activates presynaptic VPAC2 receptors to regulate inhibitory synaptic transmission within the SCN and that this effect varies from day to night.     

Effect of vasoactive intestinal polypeptide (VIP) upon myometrial blood flow in non-pregnant rabbit

Vasoactive intestinal polypeptide (VIP) containing nerve fibres have previously been demonstrated in the female genital tract of several mammalian species including the rabbit. These nerve fibres seemingly innervate vascular and non-vascular smooth muscle. For that reason we investigated the dose-relationship between VIP (5, 50, 500 pmol min^-1 kg^-1) and myometrial blood flow (MBF) using Xenon-133 washout technique. VIP increased MBF dose-dependently. VIP was on molar base 100 times more potent than acetylcholine. The action of VIP seems to be direct on vascular smooth muscle rather than mediated by other neurotransmitters, because the MBF increase was not antagonized by atropine, adrenergic blocking agents or naloxone. These findings make it likely that VIP plays a role in the local nervous control of myometrial blood flow.     

Sex differences in vasoactive intestinal peptide (VIP) concentrations in the anterior pituitary and hypothalamus of rats

Recent evidence suggests that vasoactive intestinal peptide (VIP), a putative prolactin (PRL)-releasing factor, is both synthesized and released by anterior pituitary cells, to act as a paracrine or autocrine factor. We have investigated the hypothesis that hypothalamic or pituitary VIP levels differ in male and female rats, since neuroendocrine control of PRL is sexually differentiated. Opposite sex differences were found in the hypothalamus and anterior pituitary. Random-cycle female rats had one-third higher VIP levels in the hypothalamus than males. In contrast, anterior pituitary VIP levels were 3 times as high in male rats as in females. Median eminence VIP levels were similarly low in both sexes. These results support a possible role of VIP in the sexually dimorphic regulatory mechanisms of PRL secretion. Moreover, demonstration that hypothalamic and pituitary VIP levels vary in opposite directions suggests that VIP is differentially regulated at the two sites.     

SMAO休克时肺对P物质和血管活性肠肽的清除作用

本文应用指示剂稀释技术观察了家兔ＳＭＡＯ休克时肺对＾１２５Ｉ的标记的Ｐ物质和血管活性肽的清除作用。结果表明，ＳＭＡＯ休克早期注入ＳＰ一次流经肺循环的清除率明显高于假手术对照组，Ｐ〈０．０１；注入ＶＩＰ一次流经肺循环的清除率。与假手术对照组相比无显著性差异。     

Immunomodulation of innate immune responses by vasoactive intestinal peptide (VIP): its therapeutic potential in inflammatory disease

Since the late 1970s a number of laboratories have studied the role of vasoactive intestinal peptide (VIP) in inflammation and immunity. These studies have highlighted the dramatic effect of VIP on immune cell activation and function, and studies using animal models of disease have indicated that VIP has significant therapeutic and prophylactic potential. This review will focus on the effects of VIP on innate immune cell function and discuss the therapeutic potential for VIP in inflammatory diseases of humans.     

Fasting and prolonged exercise increase vasoactive intestinal polypeptide (VIP) in plasma

6 young men had venous blood drawn during 4 experiments. The concentration of VIP in plasma increased markedly (from 1.8 (0–4.5) to 22.3 (7.8–43.8) pmol-1^?1, mean and range) during 3 h of mild bicycle exercise but not at all during an equivalent period of rest or during short term submaximal and maximal exercise. During 59 h of fasting, VIP increased from 3.6 (0.6-6.6) to 10.2 (6.6–13.8) pmol-1^?1 (p < 0.05). The concentration of glucose in plasma decreased significantly during the prolonged exercise as well as during fasting. The known metabolic actions of VIP and the demonstrated increases in its plasma concentration during negative energy balance indicate that VIP is “a polypeptide of substrate need”.     

Vagal postganglionic origin of vasoactive intestinal polypeptide (VIP) mediating the vagal tachycardia

Our aim was to confirm the role of postganglionic vagal fibres and vasoactive intestinal polypeptide (VIP) in mediating the vagal tachycardia in anaesthetised dogs. Vagal postganglionic stimulation after atenolol (1 mg/kg) and hexamethonium (10 mg/kg) caused a bradycardia (40 beats/min, n = 2), after atropine (0.5 mg/kg i.v.) the resulting tachycardia (37 beats/min) was attenuated by VIP receptor antagonism with VIP (6-28) (100 μg i.c.) by approximately 50%. VIP release from vagal postganglionic fibres mediates the vagal tachycardia.     

Fasting and prolonged exercise increase vasoactive intestinal polypeptide (VIP) in plasma.

6 young men had venous blood drawn during 4 experiments. The concentration of VIP in plasma increased markedly (from 1.8 (0--4.5) to 22.3 (7.8--43.8) pmol.1(-1), mean and range) during 3 h of mild bicycle exercise but not at all during an equivalent period of rest or during short term submaximal and maximal exercise. During 59 h of fasting, VIP increased from 3.6 (0.6--6.6) to 10.2 (6.6--13.8) pmol.1(-1) (p less than 0.05). The concentration of glucose in plasma decreased significantly during the prolonged exercise as well as during fasting. The known metabolic actions of VIP and the demonstrated increases in its plasma concentration during negative energy balance indicate that VIP is "a polypeptide of substrate need".     

Peptidergic (vasoactive intestinal peptide) nerves in the genito-urinary tract

The feline genito-urinary tract receives a rich supply of nerve fibers displaying immuno-reactivity like that of vasoactive intestinal peptide. Nerves containing vasoactive intestinal peptide are particularly numerous in the trigonum area of the bladder, around the ureteral openings and in the upper part of the urethra in both sexes, in the epididymis, prostate and vas deferens, and in the uterine cervix. Ganglia located close to or within the wall of the trigonum area and of the upper urethra contain numerous immunoreactive nerve cell bodies, which may be the origin of the fibers containing vasoactive intestinal peptide that innervate these regions.     

Upregulation of vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP) expression in stellate ganglia of children with congenital cardiovascular lesions.

The distribution patterns of vasoactive intestinal polypeptide (VIP) and calcitonin gene-related peptide (CGRP) immunoreactivities (IR) in stellate ganglia of human neonates and infants with congenital heart and vascular lesions were investigated by the method of indirect immunohistochemistry. The results demonstrated upregulation of VIP and CGRP expression in principal ganglionic neurons independently of the type of lesion. It is suggested that the activation of neuropeptide synthesis in stellate ganglia is a compensatory reaction of ganglionic neurons in response to congenital cardiovascular lesions, in regulation of heart contractility, and as a trophic influence on the ischemic myocardium. Hypoxia is the main inducing factor for the upregulation of VIP and CGRP expression in sympathetic neurons.