Urinary neurotrophic peptides in postmenopausal women with and without overactive bladder.

AIMS: The aim of this study was to compare the expression of urinary nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), substance P (SP), and calcitonin-gene related peptide (CGRP) in women with and without overactive bladder (OAB). We sought to determine factors associated with higher expression of these neuropeptides. METHODS: Participants with OAB and age-matched controls were enrolled. Symptom severity was assessed with validated questionnaires. Urinary neurotrophin levels, symptom scores, and clinical data were compared between the groups. Multivariate analysis determined independent factors associated with urinary neurotrophin levels. RESULTS: Sixty-seven women (38 OAB, 29 controls) were included. Women with OAB and controls were similar in age, race, body mass index, parity, and smoking status. Women with OAB were more likely to report a history of pelvic pain and pelvic surgery. Neurotrophic factor levels normalized to urinary creatinine did not differ between the groups. Increasing age was associated with greater urinary levels of BDNF and NGF (ß = 0.23, 95%CI 0.11-0.34 and 0.75, 95%CI 0.17-1.33, respectively, P < 0.02). Higher urinary NGF was associated with increasing BMI (ß = 0.81, 95%CI 0.05-1.57, P = 0.04) while pain was associated with elevated urinary SP (ß = 0.21, 95%CI 0.09-0.33, P = 0.001). CONCLUSIONS: Our data does not support a relationship between urinary neurotrophin levels and OAB in age-matched postmenopausal women. Further research is necessary to elucidate the role of urinary neurotrophins in the diagnosis and management of OAB. Neurourol. Urodynam. 36:740-744, 2017. © 2016 Wiley Periodicals, Inc.

Changes in urine levels of substance P, vasoactive intestinal peptide and calcitonin-gene-related peptide in patients with urinary tract infections.

Urinary tract infections (UTI) are important health problems and predisposing causes of UTI are not entirely known. Neuro-immune interactions play an important role in human health and disease. Capsaicin-sensitive sensory nerves which in nerve bladder extensively regulate immune system through neuropeptides such as substance P (SP), calcitonin-gene related peptide (CGRP) and vasoactive intestinal peptide (VIP). In addition these neuropeptides also have anti-bacterial effects. To determine how the levels of these peptides changes during UTI, 67 patients (50-90 years-old) diagnosed with UTI in Akdeniz University Faculty of Medicine Hospital were compared with 37 healthy people 50 years or older as the control group. Additionally, 7 patients with UTI symptoms (dysuria, urgency) but with sterile pyuria were also included in the study. Urine samples from 15 patients, whose symptoms regressed with control urine cultures being sterile, were taken after completion of the treatments. Urine neuropeptide levels were determined by ELISA. CGRP levels are significantly higher in patients with UTI, but did not associate with pyuria whereas SP and VIP levels were significantly lower in patients with sterile pyuria, indicating sensory nerve deficiency. Since CGRP exerts immunosuppressive effects, increased levels of the peptide may predispose to UTI. Furthermore, the connection between the observed sensory nerve deficiency and sterile pyuria warrants further studies.

The Acupuncture on Hot Flushes Among Menopausal Women (ACUFLASH) study, a randomized controlled trial.

OBJECTIVE: This study compared the effectiveness of individualized acupuncture plus self-care versus self-care alone on hot flashes and health-related quality of life in postmenopausal women. METHODS: This study involved a multicenter, pragmatic, randomized, controlled trial with two parallel arms. Participants were postmenopausal women experiencing, on average, seven or more hot flashes per 24 hours during seven consecutive days. The acupuncture group received 10 acupuncture treatment sessions and advice on self-care, and the control group received advice on self-care only. The frequency and severity (0-10 scale) of hot flashes were registered in a diary. Urine excretion of calcitonin gene-related peptide was assessed at baseline and after 12 weeks. The primary endpoint was change in mean hot flash frequency from baseline to 12 weeks. The secondary endpoint was change in health-related quality of life measured by the Women's Health Questionnaire. RESULTS: Hot flash frequency decreased by 5.8 per 24 hours in the acupuncture group (n = 134) and 3.7 per 24 hours in the control group (n = 133), a difference of 2.1 (P < 0.001). Hot flash intensity decreased by 3.2 units in the acupuncture group and 1.8 units in the control group, a difference of 1.4 (P < 0.001). The acupuncture group experienced statistically significant improvements in the vasomotor, sleep, and somatic symptoms dimensions of the Women's Health Questionnaire compared with the control group. Urine calcitonin gene-related peptide excretion remained unchanged from baseline to week 12. CONCLUSIONS: Acupuncture plus self-care can contribute to a clinically relevant reduction in hot flashes and increased health-related quality of life in postmenopausal women.

Interdependent regulation of afferent renal nerve activity and renal function: role of transient receptor potential vanilloid type 1, neurokinin 1, and calcitonin gene-related peptide receptors.

Our previous studies have shown that the activation of the transient receptor potential vanilloid type 1 (TRPV1) expressed in the renal pelvis leads to an increase in ipsilateral afferent renal nerve activity (ARNA) and contralateral renal excretory function, but the molecular mechanisms of TRPV1 action are largely unknown. This study tests the hypothesis that activation of receptors of neurokinin 1 (NK1) or calcitonin gene-related peptide (CGRP) by endogenously released substance P (SP) or CGRP following TRPV1 activation, respectively, governs TRPV1-induced increases in ARNA and renal excretory function. Capsaicin (CAP; 0.04, 0.4, and 4 nM), a selective TRPV1 agonist, administered into the renal pelvis dose-dependently increased ARNA. CAP (4 nM)-induced increases in ipsilateral ARNA or contralateral urine flow rate (Uflow) and urinary sodium excretion (UNa) were abolished by capsazepine (CAPZ), a selective TRPV1 antagonist, or 2-[1-imino-2-(2-methoxyphenyl)ethyl]-7,7-diphenyl-4-perhydroisoindolone (3aR,7aR) (RP67580) or cis-2-(diphenylmethyl)-N-[(2-iodophenyl)-methyl]-1 azabicyclo[2.2.2]octan-3-amine (L703,606), selective NK1 antagonists, but not by CGRP8-37, a selective CGRP receptor antagonist. Both SP (7.4 nM) and CGRP (0.13 muM) increased ARNA, Uflow, or UNa, and increases in these parameters induced by CGRP but not SP were abolished by CAPZ. CAP at 4 nM perfused into the renal pelvis caused the release of SP and CGRP, which was blocked by CAPZ but not by RP67580, L703,606, or CGRP8-37. Immunofluorescence results showed that NK1 receptors were expressed in sensory neurons in dorsal root ganglion and sensory nerve fibers innervating the renal pelvis. Taken together, our data indicate that NK1 activation induced by SP release upon TRPV1 activation governs TRPV1 function and that a TRPV1-dependent mechanism is operant in CGRP action.

Urinary excretion of calcitonin gene-related peptide in males with hot flushes after castration for carcinoma of the prostate.

OBJECTIVE: The majority of men who undergo surgical or medical castration due to prostatic carcinoma develop vasomotor symptoms with hot flushes. The mechanisms behind these symptoms are poorly understood. One possible explanation is a release of the vasodilatory peptide calcitonin gene-related peptide (CGRP) from perivascular nerves, which seem to be involved in the mechanisms behind vasomotion and sweating in postmenopausal women. The aim of this report was to investigate whether CGRP is involved in vasomotion in men after castration therapy. MATERIAL AND METHODS: Twenty-four hour urine excretion of CGRP was analysed in 15 men with prostatic carcinoma, using radioimmunoassay before and 3 months after surgical or medical castration. RESULTS: Eleven of the 15 men developed hot flushes during the observation period of 3 months. Twenty-four hour urine excretion of CGRP did not change significantly after castration, either in the group as a whole or in those 11 men who developed hot flushes. CONCLUSIONS: Even though we did not observe any significant changes in 24-h urine excretion of the potent vasodilator CGRP after castration it is possible that serum levels of CGRP increase during hot flushes, without having an effect on the 24-h urine excretion of the peptide.

Exercise and variations in neuropeptide concentrations in rheumatoid arthritis.

The aim of the present study was to investigate the influence of an exercise program on neuropeptide concentrations, disease activity, impairments and disabilities in rheumatoid arthritis (RA). Eleven females (median age 60 years, median disease duration 6.5 years, ARA functional classes I or II) exercised 30 min daily for 4 weeks. The urine concentrations of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) and neuropeptide Y-like immunoreactivity (NPY-LI) were analyzed 1 week prior to exercise start, at exercise start, after 2 and 4 weeks of exercise, and after a 4-week follow-up period. Measurements of disease activity, aerobic capacity, grip force, limb muscle function, and activities of daily living (ADL) were also undertaken. The results indicate a decrease (md 5.64 pM to md 3.48 pM, P

Postmenopausal women with vasomotor symptoms have increased urinary excretion of calcitonin gene-related peptide.

OBJECTIVES: To establish whether 24 h urinary excretion of the potent vasodilator calcitonin gene-related peptide (CGRP) was higher in postmenopausal women with vasomotor symptoms compared to the level in women without symptoms. We also wanted to establish whether urinary excretion of CGRP changed during the menstrual cycle in women of fertile age. MATERIAL AND METHODS: Thirteen postmenopausal women with and 13 women without vasomotor symptoms were included. Urine was collected over 24 h and CGRP excretion was measured utilizing radio-immunoassay technique. Twenty-four hour CGRP excretion was also measured in ten fertile women with regular cycles in early follicular, preovulatory and midluteal phase. RESULTS: Twenty-four hour urinary excretion of CGRP was significantly higher in women with vasomotor symptoms compared to non-flushing women (median 7.16 vs 5.15 pmol/24 h; P = 0.028). CGRP concentrations were stable throughout the ovulatory cycles. CONCLUSION: The 24 h urinary excretion of CGRP is higher in women with vasomotor symptoms than in women without these symptoms. CGRP may be the mediator of vasodilator signals originating from the thermoregulatory center.

Atrial natriuretic peptides increase calcitonin gene-related peptide within human circulation.

Long-acting natriuretic peptide (LANP), vessel dilator, and atrial natriuretic factor (ANF) (each infused at 100 ng/kg body weight [BW].min for 60 minutes) increased the circulating concentration of calcitonin gene-related peptide (CGRP) threefold to fourfold in 30 healthy humans. Within 30 minutes of stopping ANF infusion, the CGRP circulating concentration had returned to preinfusion levels, whereas its increase secondary to the other atrial peptides was still significant 2 to 3 hours after cessation of their infusions. There was a 50% decreased excretion (P < .001) of CGRP into the urine secondary to LANP and vessel dilator, which correlated with the increase of CGRP in the circulation. The ANF-induced 50% decreased CGRP excretion occurred after the circulating concentration of CGRP had returned to preinfusion levels. Kaliuretic peptide did not affect CGRP circulating concentration or excretion into urine. These data suggest that LANP and vessel dilator inhibit the metabolic breakdown of CGRP as part of their mechanism of increasing CGRP in plasma, whereas the ANF effect of increasing CGRP in plasma appears to be secondary to stimulating the release of CGRP.

Plasma concentrations and urinary excretion of regulatory peptides in patients with urticaria pigmentosa.

Patients with urticaria pigmentosa were investigated during symptom-free interval regarding plasma concentrations and urinary excretion of immunoreactive regulatory peptides: calcitonin gene-related peptide (CGRP), gastrin, neurokinin A (NKA), neuropeptide Y (NPY), somatostatin (SOM), substance P (SP) and vasoactive intestinal peptide (VIP). The plasma concentrations of these peptides, except for CGRP, were below the detection limit. The urinary excretion of the regulatory peptides were not higher in the patient group than in the controls, but in individual patients there was high urinary excretion of SP and VIP. A lower urinary excretion of CGRP was found in the patient group in addition to a tendency to a lower plasma concentration.