vasoactive-intestinal-peptide and Prostatic-Hyperplasia

Vasoactive intestinal peptide (VIP) is an important member of the group of neuropeptides that appears to be involved in the regulation of prostatic growth and function. Here we studied VIP receptors in membranes from human benign hyperplastic prostate. Accordingly to observations in rat prostatic membranes, [125I]VIP binding to human prostatic membranes suggested two classes of binding sites with high Kd = 0.22 nM) and low (Kd = 37.7 nM) affinities. VIP bound in human and rat membrane preparations to a common VIP/pituitary adenylate cyclase-activating peptide (PACAP) receptor, as VIP, PACAP-27, and PACAP-38 were equipotent for competition of [125I]VIP binding. A PACAP-preferring receptor appears to be expressed in human prostate, since [125I]PACAP binding was displaced with more potency by PACAP than by VIP, and a messenger RNA corresponding to type I PACAP receptor was found. Cross-linking experiments suggested a VIP receptor of about 71 kDa in human and 52 kDa in rat prostates. The binding of [125I]VIP to membranes and the labeling of the bands observed after electrophoresis were competitively inhibited by GTP, suggesting the coupling of VIP receptors to a G protein. Moreover, after solubilization and cross-linking, we observed a 120-kDa band that corresponded to the VIP receptor-alpha s association. VIP stimulated adenylyl cyclase activity in a dose-dependent manner, but the potency and/or the efficacy of VIP were lower in all human preparations studied than in rat prostatic membranes. In conclusion, this study clearly demonstrates the expression of VIP/PACAP common receptors associated with alpha s protein in human prostate and suggests that these neuropeptides could play an important and complex role in the physiology and pathophysiology of this human gland.

Topics: Adenylyl Cyclases; Aged; Aged, 80 and over; Animals; Base Sequence; Binding, Competitive; Cell Membrane; DNA Primers; GTP-Binding Proteins; Humans; Kinetics; Male; Molecular Sequence Data; Neuropeptides; Neurotransmitter Agents; Pituitary Adenylate Cyclase-Activating Polypeptide; Polymerase Chain Reaction; Prostate; Prostatectomy; Prostatic Hyperplasia; Radioligand Assay; Rats; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; Receptors, Pituitary Hormone; Receptors, Vasoactive Intestinal Peptide; RNA, Messenger; Transcription, Genetic; Vasoactive Intestinal Peptide

Topics: Adenylyl Cyclases; Aged; Binding, Competitive; Cell Membrane; Humans; Intercellular Signaling Peptides and Proteins; Kinetics; Male; Middle Aged; Neuropeptides; Neurotransmitter Agents; Peptides; Pituitary Adenylate Cyclase-Activating Polypeptide; Prostate; Prostatectomy; Prostatic Hyperplasia; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; Receptors, Pituitary Hormone; Receptors, Vasoactive Intestinal Peptide; Secretin; Vasoactive Intestinal Peptide

To determine the distribution of neuropeptides in male patients with bladder neck dyssynergia and benign prostatic hyperplasia.. Bladder neck tissue, obtained from male patients with bladder neck dyssynergia (BND) and control patients with benign prostatic hyperplasia (BPH), was studied immunohistochemically for protein gene product 9.5 (a general neuronal marker), vasoactive intestinal polypeptide, neuropeptide Y, calcitonin gene-related peptide, substance P, growth associated protein 43 and nitric oxide synthase.. In the bladder neck from control patients, the greatest density of nerves contained protein gene product 9.5, followed in decreasing order by neuropeptide Y; vasoactive intestinal polypeptide; calcitonin gene-related peptide; nitric oxide synthase; substance P and serotonin. The neuropeptides were found in the smooth muscle and were also associated with blood vessels. In patients with BND there was a statistically significant increase (P < 0.05) in the density of protein gene product 9.5- and neuropeptide Y-immunoreactive nerves in the smooth muscle and the base of the mucosa but not in blood vessels in the bladder neck, while the density of the other neuropeptides studied, nitric oxide synthase and serotonin did not significantly change from that of control tissue. Growth associated protein 43-immunoreactive nerves were absent from the bladder neck from both groups of patients.. It is suggested that the increase in density of protein gene product 9.5- and neuropeptide Y-immunoreactive nerves, part of the sympathetic contractile system of the bladder neck, may exacerbate bladder outlet obstruction and thus play a role in the pathogenesis of BND.

Topics: Adult; Amino Acid Oxidoreductases; Calcitonin Gene-Related Peptide; Humans; Immunohistochemistry; Male; Nerve Tissue Proteins; Neurons; Neuropeptide Y; Nitric Oxide Synthase; Prostatic Hyperplasia; Substance P; Thiolester Hydrolases; Ubiquitin Thiolesterase; Urinary Bladder; Urinary Bladder Neck Obstruction; Vasoactive Intestinal Peptide

Different regions of the prostate gland, namely prostatic capsule, peripheral prostate and central prostate (subdivided into proximal (near the bladder neck), distal (near the verumontanum) and midway between these areas) were obtained from 32 obstructed (stable obstructed, n = 8; unstable obstructed, n = 13; acute retention, n = 11) and five control patients. The innervation of these tissues was studied both histochemically to localise acetylcholinesterase activity and immunohistochemically for dopamine-beta-hydroxylase, 5-hydroxytryptamine, vasoactive intestinal polypeptide, neuropeptide Y, leu- and met-enkephalin, calcitonin gene-related peptide, substance P and somatostatin. In control patients the greatest density of nerves was found in the proximal central prostate, followed by the anterior capsule and distal central prostate, with the least density in the peripheral prostate. The greatest density of nerves were acetylcholinesterase positive and immunoreactive to neuropeptide Y followed (in decreasing order) by nerves immunoreactive to: vasoactive intestinal polypeptide and dopamine beta-hydroxylase; leu-enkephalin and 5-hydroxytryptamine; calcitonin gene-related peptide; met-enkephalin; substance P; somatostatin. In addition a group of periacinar 5-hydroxytryptamine-immunoreactive cells and ganglia containing acetylcholinesterase, dopamine beta-hydroxylase and all of the peptides studied except somatostatin were identified. In the prostate gland from obstructed patients there was a significant reduction in the density of acetylcholinesterase-positive nerves (p less than 0.001) when compared with the controls. A similar trend was found for dopamine beta-hydroxylase, 5-hydroxytryptamine and all of the putative neuropeptides in most areas of the prostate, the most notable exceptions being in the peripheral prostate, with an increase in dopamine beta-hydroxylase- and leu-enkephalin-immunoreactive nerves in all three groups of obstructed patients an an increase in vasoactive intestinal polypeptide- and calcitonin gene-related peptide-immunoreactive nerves in those presenting in urinary retention. The functional significance of these findings is discussed.

Topics: Acetylcholinesterase; Aged; Calcitonin Gene-Related Peptide; Dopamine beta-Hydroxylase; Enkephalin, Leucine; Enkephalin, Methionine; Humans; Male; Nerve Fibers; Neuropeptide Y; Prostate; Prostatic Hyperplasia; Serotonin; Urinary Bladder Neck Obstruction; Vasoactive Intestinal Peptide

In order to evaluate a possible role of several peptides in the human urogenital tract, peptide concentrations in urogenital tissues collected from surgery were measured using specific radioimmunoassay. The specimens were extracted in boiling 0.5M acetic acid, and these extracts were utilized to measure neuropeptide concentrations, i.e., neuropeptide Y(NPY), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP) and peptide 7B2. The highest concentrations of NPY were found in seminal vesicle (145 +/- 42pmol/g) and vas deference (104 +/- 26pmol/g). There was no significant difference in NPY concentration between malignant and non-malignant tissues (prostate and urinary bladder). High concentrations of VIP were also observed in several urogenital tissues (seminal vesicle, vas deference and urethra). VIP concentrations in prostatic cancer and carcinoma of urinary bladder seemed to be reduced, though no significant difference could be found in each corresponding tissue. Pituitary peptide 7B2 was found to be present in the human urogenital tract in relatively low concentrations. A significant difference was observed in CGRP concentration between carcinoma of urinary bladder and adjacent normal vesicular tissues (p less than 0.05). These four peptide immunoreactivities were further characterized by gel permeation or high performance liquid chromatography. Each main immunoreactivity in urogenital extracts seemed to correspond to each synthetic standard or pituitary extracts (in case of 7B2). These results demonstrated that pituitary peptide 7B2 was shown to be present in the human urogenital tract and that the distribution patterns of these peptides might correlate to their pathophysiological role in the urogenital tract. Furthermore, the absence of CGRP immunoreactivity in carcinoma of urinary bladder may be useful for additional diagnostic information.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Chromatography, Gel; Chromatography, High Pressure Liquid; Female; Humans; Male; Middle Aged; Nerve Tissue Proteins; Neuroendocrine Secretory Protein 7B2; Neuropeptide Y; Neuropeptides; Pituitary Hormones; Prostatic Hyperplasia; Prostatic Neoplasms; Radioimmunoassay; Urinary Bladder Neoplasms; Urogenital Neoplasms; Urogenital System; Vasoactive Intestinal Peptide

Three human studies were performed to evaluate the influence of vasoactive intestinal polypeptide (VIP) on bladder and urethral function. Bladder neck smooth muscle biopsies were obtained from nine men with functional bladder neck obstruction, from 10 men with medium sized benign prostatic hypertrophy and from four patients with a normal infravesical outlet. The biopsies were analysed for VIP by radioimmunoassay and by immunohistochemistry. No differences were found between the groups. Pressure-flow-EMG studies were performed in five men and urethrocystometry was performed in six women at rest, repeated coughing and at squeezing before, during and after VIP 3 micrograms/kg X h intravenously. No systematic changes developed in any of the urodynamic parameters.

Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Muscle, Smooth; Prostatic Hyperplasia; Urethra; Urinary Bladder; Urinary Bladder Neck Obstruction; Urination; Urodynamics; Vasoactive Intestinal Peptide

The rat ventral prostate and the human hyperplastic prostate contain adenylyl cyclases which can be activated by a variety of neurotransmittors, including vasoactive intestinal peptide (VIP), beta 2 adrenergic agonists, and dopamine. In both species the response to VIP was predominantly localized to the epithelial fraction. In the human tissue activation of the enzyme could also be achieved with prostaglandin E1 (PGE1) and an alpha 2 adrenergic agonist both associated with the stromal compartment. Castration in the rat caused a marked reduction in the basal activity of the enzyme and the maximal level of the hormone-stimulated response per cell (per mg DNA), but had only minor effects on the pattern of activation when expressed per mg membrane protein. Androgen treatment (dihydrotestosterone propionate, 2.5 mg/day) prevented the castration effects. Estrogen treatment (estradiol benzoate, 125 micrograms/day) could not prevent the castrational changes but maintained enzyme activity at a level above that of the castrate. There were no major qualitative differences in the pattern of activation of the cyclase between the different lobes of the rat prostate and the seminal vesicle.

Topics: Adenylyl Cyclases; Alprostadil; Animals; Clonidine; Dopamine; Enzyme Activation; Histamine; Humans; Isoproterenol; Male; Orchiectomy; Propanolamines; Prostate; Prostatic Hyperplasia; Rats; Rats, Inbred Strains; Seminal Vesicles; Terbutaline; Vasoactive Intestinal Peptide