Role Of Sensory Neuropeptides Research Articles

The role of sensory neuropeptides in motor innervation of the hamster isolated urinary bladder.

In this study we have characterized the role of sensory fibers and of the sensory peptides, neurokinin A (NKA) and calcitonin gene-related peptide (CGRP), on the contractile responses evoked by single pulse electrical field stimulation (EFS) in the hamster urinary bladder. EFS of the hamster isolated urinary bladder produced twitch contractions which were unaffected by atropine but abolished by tetrodotoxin. The P2 purinoreceptor antagonist PPADS (30 microM) inhibited twitches by 66+/-4% on its own and by 78+/-3% in the presence of atropine. The selective tachykinin NK2 receptor antagonist nepadutant produced a slight but consistent reduction of twitch amplitude (-21+/-3%) at 1 microM. Addition of nepadutant to atropine and PPADS did not further increase their inhibitory effect. The application of hCGRP (10-300 nM) produced a concentration-dependent inhibition of twitches (Emax -38+/-3%, EC50=12 nM) and a small reduction of tone (0.5+/-0.09 mN). Similar effects were obtained with capsaicin (0.1-10 microM) which inhibited EFS-evoked contractions with an EC50 of 100.0 nM and a maximal effect of 34+/-4% inhibition at 1 microM. Under submaximal parameters of stimulation NKA (10 nM) increased the amplitude of twitches by 45+/-6% and produced a concentration-dependent tonic contraction (EC50=55.9 nM). The CGRP1 receptor subtype antagonist, hCGRP(8-37), increased by 29+/-8% the EFS-evoked contractions and significantly reduced the response to 0.1 microM CGRP. Capsaicin (10 microM) increased both CGRP-LI and NKA-LI release from superfused slices of hamster urinary bladder by about sixfold and by about 70%, over baseline, respectively. A second application of capsaicin was ineffective, indicating a complete desensitization of sensory nerve efferent function. In the hamster urinary bladder the sensory neuropeptides NKA and CGRP are co-released by sensory fibers after stimulation either by EFS or capsaicin. However, the role of CGRP appears functionally predominant.

The role of sensory neuropeptides and nitric oxide on pulpal blood flow and tissue pressure in the ferret.

A study was designed to investigate the effects of close intra-arterial infusion of antagonists to the sensory neuropeptides calcitonin gene-related peptide and substance P, as well as the effect of the nitric oxide synthesis inhibitor L-NAME on pulpal blood flow and interstitial fluid pressure during resting conditions and after electrical tooth stimulation. The micropuncture technique was used to measure tissue pressure and laser-Doppler flowmetry for blood flow recordings in ferret canine teeth. Close intra-arterial infusion of antagonists to calcitonin gene-related peptide and substance P significantly reduced resting blood flow (p < 0.05) and interstitial fluid pressure (p < 0.005) by unchanged systemic arterial pressure, while L-NAME administration caused a significant rise in interstitial fluid pressure (p < 0.05) and systemic arterial pressure (p < 0.005), with a concomitant fall in resting blood flow (p < 0.005). Tooth stimulation after calcitonin gene-related peptide antagonist infusion gave no significant change in blood flow or interstitial fluid pressure, whereas substance P antagonist infusion only partly eliminated the vasodilator response. L-NAME had no effect on the vasodilation induced by tooth stimulation. It is concluded that a resting vasodilator tone due to release of calcitonin gene-related peptide, substance P, and nitric oxide exists in the ferret dental pulp. The sensory neuropeptides exert their effect predominantly on pre-capillary vessels, and nitric oxide predominantly on post-capillary vessels. The sensory neuropeptide calcitonin gene-related peptide seems to be mainly responsible for the increase in blood flow and interstitial fluid pressure during tooth stimulation, whereas there was no evidence that nitric oxide participates in the vasodilation induced by tooth stimulation.

Role of sensory neuropeptides in post-allergic propranolol-induced bronchoconstriction in guinea pigs in vivo

Role of sensory neuropeptides in post-allergic propranolol-induced bronchoconstriction in guinea pigs in vivo

Role of sensory neuropeptides in post‐allergic propranolol‐induced bronchoconstriction in guinea pigs in vivo

Administration of propranolol can provoke bronchoconstriction in asthmatic patients. We hypothesized that such bronchoconstriction may result from the inflammatory mediators released by an allergic reaction. We recently developed a guinea pig model for propranolol-induced bronchoconstriction (PIB). Neuropeptides which are released from C-fibre nerve endings have been postulated to induce bronchial hyperresponsiveness through neurogenic inflammation. The purpose of this study was to examine whether sensory neuropeptides are involved in the development of PIB after allergic reaction. Propranolol at a concentration of 10 mg/ml was inhaled 20 min after antigen challenge in passively sensitized, anaesthetized and artificially ventilated guinea pigs. The animals were treated intravenously with a NK1 and NK2 dual antagonist, FK224, in a dose of 1 or 10 mg/kg or vehicle or a selective NK1 antagonist, FK888, in a dose of 1 or 10 mg/kg or vehicle 10 min before or 15 min after antigen challenge. Propranolol inhaled 20 min after antigen challenge caused bronchoconstriction. FK224 or FK888 administered 15 min after antigen challenge as well as 10 min before antigen challenge did not reduce the PIB. We conclude that neuropeptides such as neurokinin A and substance P do not directly contribute to the development of PIB after allergic reaction.

The Role of Sensory Neuropeptides in Airway Hyperresponsiveness

The Role of Sensory Neuropeptides in Airway Hyperresponsiveness

Antigen-induced airway hyperresponsiveness is associated with airway tissue NEP hypoactivity in rats

In the present study, the role of sensory neuropeptides in the airway hyperresponsiveness (AHR) was investigated. First, the effect of the depletion of sensory neuropeptides by systemic capsaicin treatment on the AHR to acetylcholine (ACh) induced by repeated antigenic challenge to sensitized rats was studied. We secondly investigated whether the neutral endopeptidase (NEP) activity was altered at the antigen-induced AHR. Male Wistar rats were sensitized and repeatedly challenged with DNP- Ascaris antigen. Twenty-four hours after the last antigenic challenge, a marked AHR to inhaled ACh (0.001–0.03%) was observed. This AHR was significantly attenuated by systemic capsaicin pretreatment prior to sensitization. On the other hand, in normal rats, the airway responsiveness to inhaled ACh was significantly increased by pretreatment with NEP inhibitor, phosphoramidon (3 mg/kg, i.v.), but the NEP inhibitor-induced effect was no more observed in the antigen-induced AHR rats. Furthermore, it was found that the airway NEP activity was significantly decreased at the antigen-induced AHR. These findings suggest that NEP hypoactivity and resultant increased sensory neuropeptides have an important role in the pathogenesis of antigen-induced AHR in rats.

O-52 - Pharmacological studies on the respiratory tract (Rept. 171): Role of sensory neuropeptides in airway hyperresponsiveness in rats.

O-52 - Pharmacological studies on the respiratory tract (Rept. 171): Role of sensory neuropeptides in airway hyperresponsiveness in rats.

Ganglion-blocking agents enhance neurally mediated bronchoconstriction in the guinea-pig: possible role of sensory neuropeptides

The effect of ganglion blockade by hexamethonium bromide (0.1–100 μmol · kg −1) and pentolinium tartrate (0.01–3 μmol · kg −1) on the bronchoconstriction induced by vagal nerve stimulation (15 HZ, 0.2 ms, 3 s, 7–20 V) was evaluated in the anaesthetized guinea-pig. Both ganglion-blocking agents potentiated this response dose dependently. When the neural bronchoconstriction was suppressed by atropine, hexamethonium restored this response dose dependently. Hexamethonium produced inhibitory effects on vagally induced bronchoconstriction in capsaicin-desensitized and in propranolol- or reserpine-pretreated guinea-pigs. Propranolol (0.03–3 μmol · kg −1) produced a marked dose-dependent increase of neural bronchoconstriction (which was markedly reduced, about 10 times) in capsaicin-desensitized animals. Our results show that ganglion-blocking agents potentiate neural bronchoconstriction in the guinea-pig and that sensory neuropeptides may have a role in this effect. Moreover, β-adrenergic modulation of the release of neuropeptides from vagal sensory fibers is suggested.

Airway hyperreactivity induced by active cigarette smoke exposure in guinea-pigs: possible role of sensory neuropeptides

Exposure to cigarette smoke is associated with increased airway responsiveness to different stimuli, both in human and animal studies. However, the mechanisms involved in the pathogenesis of smoke-induced airway hyperreactivity are less clear. We investigated the development of airway hyperreactivity induced by active cigarette smoke exposure in anaesthetised guinea-pigs and the possible mechanisms involved. Active inhalation of cigarette smoke (15 s/min for 10 min) potentiated the bronchocontractile effect of acetylcholine (Ach), indicating the occurrence of airway hyperreactivity. This phenomenon appeared within 5 min and lasted up to 50 min after smoke exposure. Smoke induced airway hyperreactivity was a non-specific phenomenon, involving an enhanced responsiveness to both Ach and histamine (Hist). Recruitment of proinflammatory cells into the airway lumen, as revealed by the analysis of bronchoalveolar lavage fluid, paralleled the development of the hyperreactive phenomenon, suggesting a relationship between the inflammatory reaction and the genesis of smoke-induced airway hyperreactivity. Cervical bilateral vagotomy did not modify either the degree and the time-course of smoke induced airway hyperreactivity. Moreover, atropine treatment did not affect the increase in Hist response due to smoke inhalation. On the other hand, depletion of substance P due to capsaicin pretreatment almost completely prevented the capacity of cigarette smoke to potentiate Ach induced bronchoconstriction. Cyclo-oxygenase inhibition, by indomethacin pretreatment, reduced the time course of the hyperreactivity induced by smoke inhalation. Our results clearly demonstrate the occurrence of airway hyperreactivity triggered by active cigarette smoke exposure. Moreover, the data obtained suggest a predominant role for substance P and related peptides in the pathogenesis of smoke induced increase in airway responsiveness.