Localisation and measurement of VIP in the genitourinary system of man and animals

doi:10.1016/0196-9781(84)90211-0

Peptides

Volume 5, Issue 2, March–April 1984, Pages 225-230

https://doi.org/10.1016/0196-9781(84)90211-0 Get rights and content

Abstract

VIP is present in the genitourinary system of man and animals. In man the highest concentrations are found in the penis, the uterus and vagina and in the urinary bladder. VIP nerves heavily innervate the erectile tissue of the male external genitalia, the uterine smooth muscle and blood vessels, the seromucous glands of the cervix, and the lamina propria and vaginal epithelium. In the urinary bladder, VIP nerves are located beneath the transitional epithelium, in the lamina propria and in the smooth muscle. Other areas well innervated by VIP nerves include the prostate, seminal vesicles and vasa deferentia. Chemical (phenol- and 6-OHDA) or surgical (hypogastric or pelvic nerve section) extrinsic denervation fail to deplete the genitourinary system of its VIP content, supporting the view that VIP-containing nerves originate from local ganglion cells. Indeed, neuronal cell bodies containing VIP are seen in the paracervical ganglia of the female genitalia, the para- or intramural bladder ganglia and scattered through the base of the cavernosum body, the neck of the bladder and the prostate. The finding of elevated levels of VIP in the local circulation after induced penile erection in man and mammals and the ability of VIP to relax the detrusor muscle of the bladder suggests that the peptide may be involved in penile erection and bladder relaxation, as does the marked VIP depletion in the penis or bladder in patients suffering from diabetic impotence or bladder instability.

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Cited by (59)

Neuronal control of the vagina in vertebrates: A review
2023, Acta Histochemica
Citation Excerpt :
These ganglia receive the pelvic nerves at their dorsal edge, the cavernous nerve at their most caudal corner, the hypogastric nerve at their cranial edge, and the accessory nerves at their ventral edge (Bertrand and Keast, 2020). Nitrergic axons, and NPY-, VIP- and PACAP-containing nerve terminals to the vaginal wall also occur (Huang et al., 1984; Giraldi et al., 2002; Polak and Bloom, 1984; Ting et al., 2004). The rodent vagina contains less VIPergic nerves than the human vagina, and they do not contact the epithelium (Alm et al., 1980b; Papka et al., 1985), as observed in human (Hilliges et al., 1995; Ting et al., 2004).
At present, there is an increased interest in the vaginal microbiome. It is believed that microbes play equally important roles in the vagina, including the modulation of neuronal pathways, as in the gut. However, in man as well as in animals, the vagina is the least well-studied part of the female reproductive system. The vagina, a fibromuscular tract, having two main functions, i.e., childbirth and sexual intercourse, is mainly innervated by the pudendal nerve and the pelvic splanchnic nerves (the uterovaginal nerve plexus) containing sympathetic, parasympathetic and nociceptive nerve fibers. Innervation density in the vaginal wall undergoes significant remodeling due to hormonally mediated physiological activity. Knowledge about expression and function of neuropeptides and neurotransmitters in the vaginal fibers is incomplete or not established. Most research concerning the neuroregulation of the vagina and the function and expression of neuropeptides and neurotransmitters, is performed in several vertebrate species, including large farm animals, rodents, domestic fowl and lizards.
This review summarizes, on a bibliographic basis, the current knowledge on vaginal innervation and function of neuropeptides and neurotransmitters expressed in vaginal nerve fibers in several vertebrate species, including humans. The presence and role played by the local microbioma is also explored.
A thorough knowledge of the vaginal innervation is necessary to unravel the putative communication of the vaginal microbiome and vaginal nerve fibers, but also to understand the effects of vaginal pathologies and of administered drugs on the neuroregulation of the vagina.
Estrogen and female reproductive tract innervation: Cellular and molecular mechanisms of autonomic neuroplasticity
2015, Autonomic Neuroscience: Basic and Clinical
Citation Excerpt :
In contrast, pelvic and vagal parasympathetic neurectomy is not involved in the final remodeling of the cervix at term. In the rat, vaginal innervation is composed of sympathetic nerves, cholinergic parasympathetic nerves immunoreactive for vesicular acetylcholine transporter (VAChT), NOS-ir axons, and NPY-, VIP- and PACAP-ir terminals (Huang et al., 1984; Polak et al., 1984; Giraldi et al., 2002; Ting et al., 2004). In pigs and cows, NOS frequently co-localizes with SP and VIP (Majewski et al., 1995).
The female reproductive tract undergoes remarkable functional and structural changes associated with cycling, conception and pregnancy, and it is likely advantageous to both individual and species to alter relationships between reproductive tissues and innervation. For several decades, it has been appreciated that the mammalian uterus undergoes massive sympathetic axon depletion in late pregnancy, possibly representing an adaptation to promote smooth muscle quiescence and sustained blood flow. Innervation to other structures such as cervix and vagina also undergo pregnancy-related changes in innervation that may facilitate parturition. These tissues provide highly tractable models for examining cellular and molecular mechanisms underlying peripheral nervous system plasticity. Studies show that estrogen elicits rapid degeneration of sympathetic terminal axons in myometrium, which regenerate under low-estrogen conditions. Degeneration is mediated by the target tissue: under estrogen's influence, the myometrium produces proteins repulsive to sympathetic axons including BDNF, neurotrimin, semaphorins, and pro-NGF, and extracellular matrix components are remodeled. Interestingly, nerve depletion does not involve diminished levels of classical sympathetic neurotrophins that promote axon growth. Estrogen also affects sympathetic neuron neurotrophin receptor expression in ways that appear to favor pro-degenerative effects of the target tissue. In contrast to the uterus, estrogen depletes vaginal autonomic and nociceptive axons, with the latter driven in part by estrogen-induced suppression of BMP4 synthesis. These findings illustrate that hormonally mediated physiological plasticity is a highly complex phenomenon involving multiple, predominantly repulsive target-derived factors acting in concert to achieve rapid and selective reductions in innervation.
Visceral Motoneurons
2012, The Mouse Nervous System
Precise motor control of visceral effector tissues, including exocrine and endocrine glands, vascular and visceral smooth muscle, adipose tissue, and cardiac muscle is essential for survival of the individual and for successful reproduction. These diverse tissue types are controlled by separate anatomical and functional pathways. These “autonomic pathways” can be activated independently or co-activated depending on the specific reflex or environmental challenge encountered. Overarching drives for activation of autonomic pathways are varied but include: adjusting vascular perfusion to tissues according to their specific requirements, maintenance of chemical gradients, energy balance, thermoregulation, and reproductive behaviors. This omits many other autonomic responses such as tear formation and regulation of pupil diameter. Above drives apply to all vertebrates, and to some extent the general anatomical and functional operation of visceromotor pathways are conserved across species. The parasympathetic, sympathetic and enteric divisions of the autonomic nervous system are best understood in the context of their anatomical projections. Peripheral autonomic motor pathways consist of a final central nervous system (CNS) neuron that sends an axon via either cranial or spinal nerves to synapse with a neuron in a peripheral ganglion which innervates the final target. The available data on peripheral autonomic pathways in mice indicates that neurotransmitter phenotype and neuroeffector transmission is broadly similar to that observed in rats and other experimental animals. There are, however, aspects of neuroanatomy, in particular the expression of some chemical markers, which differ, not only between rat and mouse, but between strains of mice. Clearly there is scope for further immunohistochemical and retrograde tracing studies to ascertain which of these differences has any functional significance. Postganglionic autonomic neurons show the same target-related morphological trends as homologous neurons in larger mammals.
Autonomic control of the urogenital tract
2011, Autonomic Neuroscience: Basic and Clinical
Citation Excerpt :
Axons containing catecholamines or immunoreactivity to tyrosine hydroxylase are associated with vascular and non-vascular smooth muscle in the wall of the uterus, cervix and vagina of all species studies (Owman and Sjöberg, 1966; Papka et al., 1985). Axons immunoreactive for ChAT, VIP and or nNOS are found in the female reproductive tract (Papka et al., 1995, 1999; Polak and Bloom, 1984). Many of these arise from neurons in paracervical ganglia, but others are probably sensory axons (Papka et al., 1995).
The urogenital tract houses many of the organs that play a major role in homeostasis, in particular those that control water and salt balance, and reproductive function. This review focuses on the anatomical and functional innervation of the kidneys, urinary ducts and bladders of the urinary system, and the gonads, gonadal ducts, and intromittent organs of the reproductive tract. The literature, especially in recent years, is overwhelmingly skewed toward the situation in mammals. Nevertheless, where specific neurochemical markers have been investigated, common patterns of innervation can be found in representatives from most vertebrate classes. Not surprisingly the vasculature, epithelia and smooth muscle of all urogenital organs receives adrenergic innervation. These nerves may contain non-adrenergic non-cholinergic (NANC) neurotransmitters such as ATP and NPY. Cholinergic nerves increase motility in most urogenital organs with the exception of the kidney. The major NANC nerves found to influence urogenital organs include those containing VIP/PACAP, galanin and neuronal nitric oxide synthase. These can be found associated with both smooth muscle and epithelia. The role these nerves play, and the circumstances where they are activated are for the most part unknown.
Visceral Motoneurons
2011, The Mouse Nervous System
Precise motor control of visceral effector tissues, including exocrine and endocrine glands, vascular and visceral smooth muscle, adipose tissue, and cardiac muscle is essential for survival of the individual and for successful reproduction. These diverse tissue types are controlled by separate anatomical and functional pathways. These “autonomic pathways” can be activated independently or co-activated depending on the specific reflex or environmental challenge encountered. Overarching drives for activation of autonomic pathways are varied but include: adjusting vascular perfusion to tissues according to their specific requirements, maintenance of chemical gradients, energy balance, thermoregulation, and reproductive behaviors. This omits many other autonomic responses such as tear formation and regulation of pupil diameter. Above drives apply to all vertebrates, and to some extent the general anatomical and functional operation of visceromotor pathways are conserved across species. The parasympathetic, sympathetic and enteric divisions of the autonomic nervous system are best understood in the context of their anatomical projections. Peripheral autonomic motor pathways consist of a final central nervous system (CNS) neuron that sends an axon via either cranial or spinal nerves to synapse with a neuron in a peripheral ganglion which innervates the final target. The available data on peripheral autonomic pathways in mice indicates that neurotransmitter phenotype and neuroeffector transmission is broadly similar to that observed in rats and other experimental animals. There are, however, aspects of neuroanatomy, in particular the expression of some chemical markers, which differ, not only between rat and mouse, but between strains of mice. Clearly there is scope for further immunohistochemical and retrograde tracing studies to ascertain which of these differences has any functional significance. Postganglionic autonomic neurons show the same target-related morphological trends as homologous neurons in larger mammals.
Vasoactive intestinal peptide (VIP) induces malignant transformation of the human prostate epithelial cell line RWPE-1
2010, Cancer Letters
Citation Excerpt :
As deregulated MMP expression and increased cellular ROS are characteristic of both fibrosis and malignancy, it suggests that increased MMP expression may stimulate fibrosis, tumorigenesis, and tumor progression by inducing transdifferentiation of epithelial cells into activated myofibroblasts [15]. Vasoactive intestinal peptide (VIP), a neuropeptide present in the human prostate gland, is secreted by autonomous nerves [16] and produced by prostate cells [17]. VIP exerts a wide range of biological effects acting through VPAC1 and VPAC2 receptors.
The carcinogenic potential of vasoactive intestinal peptide (VIP) was analyzed in non-tumor human prostate epithelial cells (RWPE-1) and in vivo xenografts. VIP induced morphological changes and a migratory phenotype consistent with stimulation of expression/activity of metalloproteinases MMP-2 and MMP-9, decreased E-cadherin-mediated cell–cell adhesion, and increased cell motility. VIP increased cyclin D1 expression and cell proliferation that was blocked after VPAC₁-receptor siRNA transfection. Similar effects were seen in RWPE-1 tumors developed by subcutaneous injection of VIP-treated cells in athymic nude mice. VIP acts as a cytokine in RWPE-1 cell transformation conceivably through epithelial–mesenchymal transition (EMT), reinforcing VIP role in prostate tumorigenesis.

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Embryologic development, morphologic aspects and distributionLocalisation and measurement of VIP in the genitourinary system of man and animals

Abstract

Neuroscience

J Urol

Life Sci

Lancet

Vasoactive intestinal polypeptide nerves in the human female genital tract

Am J Obstet Gynecol

Origin and distribution of VIP (vasoactive intestinal polypeptide) nerves in the genito-urinary tract

Cell Tissue Res

Radioimmunoassay of Gut Regulatory Peptides

Vasoactive intestinal polypeptide in tissue of the human female reproductive tract

Am J Obstet Gynecol

Measurement of VIP and origin of its innervation in the rat urinary bladder

Repeated applications of first layer antiserum improves immunostaining, a modification of indirect immunofluorescence procedure

Histochem J

Vasoactive intestinal polypeptide in the normal and unstable bladder

Br J Urol

Vasoactive intestinal polypeptide in (VIP) the human female reproductive tract: distribution and motor effect

Biol Reprod

Embryologic development, morphologic aspects and distribution
Localisation and measurement of VIP in the genitourinary system of man and animals