Hydrogen sulfide (H₂S) stimulates capsaicin‐sensitive primary afferent neurons in the rat urinary bladder

Abstract

In the rat isolated urinary bladder, NaHS (30 mM-3 mM) and capsaicin (10 nM-3 mM) produced concentration-dependent contractile responses (pEC 50 ¼ 3.570.02 and 7.170.02, respectively) undergoing dramatic tachyphylaxis. In preparations in which sensory nerves were rendered desensitized (defunctionalized) by high-capsaicin (10 mM for 15 min) pretreatment, neither capsaicin itself nor NaHS produced any motor effect. NaHS-induced contractile effects were totally prevented by the simultaneous incubation with tachykinin NK 1 (GR 82334; 10 mM) and NK 2 (nepadutant; 0.3 mM) receptor-selective antagonists. Tetrodotoxin (1 mM) only partially reduced the response to NaHS. These results provide pharmacological evidence that H 2 S stimulates capsaicin-sensitive primary afferent nerve terminals, from which tachykinins are released to produce the observed contraction by activating NK 1 and NK 2 receptors. While the molecular site of action of H 2 S remains to be investigated, our discovery may have important physiological significance since H 2 S concentrations capable of stimulating sensory nerves overlap those occurring in mammalian tissues under normal conditions.

Hydrogen sulfide and inflammation: the good, the bad, the ugly and the promising

“…Furthermore, in the isolated guinea pig airway, NaSH induced the release of SP and CGRP from sensory nerve terminals, and led to airway constriction through capsaicin and NKR1/NKR2-transient receptor potential vanilloid 1 (TRPV1)-dependent pathways [73,74]. Similarly, in isolated rat bladder [75] and rat detrusor muscle [76], NaSH induced tachykin release from caspaicin-sensitive primary afferent neurons, leading to smooth muscle contraction. Collectively, these studies suggest that induction of neurogenic inflammation could mediate the reported proinflammatory role of H 2 S in inflammatory pathologies.…”

Hydrogen sulphide: an endogenous stimulant of capsaicin‐sensitive primary afferent neurons?

“…In the present issue, Patacchini et al (2004) present evidence that in the detrusor muscle of the rat urinary bladder H 2 S produced contractile responses. These responses exhibited marked tachyphylaxis similar to responses to capsaicin, the active principle from chillies that stimulates certain primary afferent neurons to release neuropeptides, in particular tachykinins and calcitonin gene-related peptide (CGRP) (Maggi, 1995).…”

“…From the results reported by Patacchini et al (2004), the site of action of H 2 S cannot be determined with certainty. However, the observation that the responses to H 2 S exhibited a similar resistance to tetrodotoxin as those to capsaicin indicates that H 2 S predominantly activates the primary afferent nerve terminals directly rather than indirectly via axonal conduction, which involves fast tetrodotoxin-sensitive sodium channels.…”

“…Thus capsaicin may produce stimulation of some smooth muscles and relaxation of others. Therefore, previous studies on the actions of H 2 S, such as its vasorelaxant effect, may need re-evaluation in light of the findings reported by Patacchini et al (2004) Patacchini et al (2004) has opened a new field of research into the pharmacology of H 2 S and of primary afferent neurons, which should lead to new advances in understanding the physiological and pathophysiological roles of this putative endogenous gaseous neurotransmitter.…”

Effects of Hydrogen Sulfide on Alternative Pathway Respiration and Induction of Alternative Oxidase Gene Expression in Rice Suspension Cells

“…Hydrogen sulfi de (H 2 S) is a well-known gas characterized by a peculiar rotten egg smell, representing a primary chemical hazard in natural gas production, in sewage treatment, and in certain industrial manufacturings (Patacchini et al, 2004). Hydrogen sulfi de is recognized to be a potent inhibitor of cytochrome c oxidase, the terminal enzyme of oxidative phosphorylation, and this is generally considered to be its primary mechanism of toxicity in animals (Reiffenstein et al, 1992;Dorman et al, 2002) and in plants (Kumazawa, 1984).…”