Tachykinins and calcitonin gene-related peptide (CGRP) as co-transmitters released from peripheral endings of sensory nerves

Maggi, Carlo Alberto

doi:10.1016/0301-0082(94)e0017-b

Cited by 418 publications

(300 citation statements)

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“…The ability of capsaicin to produce smooth muscle excitatory and/or inhibitory effects by activating the local efferent function of capsaicin-sensitive sensory nerves has widely been investigated by our and other groups (Holzer, 1991;Maggi, 1995, for reviews). In particular, in the rat urinary bladder capsaicin produces excitatory motor responses that are mediated by tachykinins (mainly substance P, and neurokinin A) released from the activated sensory nerve terminals (Maggi et al, 1991).…”

Section: Resultsmentioning

confidence: 99%

“…Tachykinins, in turn, stimulate tachykinin NK 1 and NK 2 receptors present on detrusor smooth muscle cells to produce the observed contractile response to capsaicin (Maggi et al, 1991). One peculiar feature of capsaicin action is that the excitatory effects produced by this drug are followed by desensitization of sensory nerves, which become progressively less responsive to capsaicin itself and other activating stimuli (Maggi, 1995). In particular, the in vitro exposure of rat detrusor smooth muscle to capsaicin (10 mM) for 15 min renders the preparations totally unresponsive to further capsaicin administration (Patacchini et al, 1990).…”

Section: Resultsmentioning

confidence: 99%

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

Patacchini

Santicioli

Giuliani

et al. 2004

British J Pharmacology

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

Patacchini

Santicioli

Giuliani

et al. 2004

British J Pharmacology

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103

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“…The family of neurokinin receptors NK 1 , NK 2 and NK 3 are G-protein coupled receptors which activate phospholipase C (Maggi, 1995(Maggi, ,1997b. The breakdown of phospholipids into diacylglycerol by PLC, activates PKC (Torrens et al, 1997) to phosphorylate and inhibit a number of K + channels (Boland and Jackson, 1999,Hagiwara et al, 2003,Richardson and Vasko, 2002.…”

Section: Discussionmentioning

confidence: 99%

Neurokinins enhance excitability in capsaicin-responsive DRG neurons

Sculptoreanu

Groat

2007

Experimental Neurology

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Neurokinins released by capsaicin-responsive (C-R) dorsal root ganglia neurons (DRG) may control firing in these neurons by an autofeedback mechanism. Here we used patch clamp techniques to examine the effects of neurokinins on firing properties of dissociated DRG neurons of male rats. In C-R neurons that generated only a few action potentials (APs, termed phasic) in response to long depolarizing current pulses (600 ms), substance P (SP, 0.5 μM) lowered the AP threshold by 11.0 ±0.3 mV and increased firing from 1.1±0.7 APs to 5.2±0.6 APs. In C-R tonic neurons that fire multiple APs, SP elicited smaller changes in AP threshold (6.0±0.1 mV reduction) and the number of APs (11±1 vs. 9±1 in control). The effects of SP were similar to the effect of heteropodatoxin II (0.05 μM) or low concentrations of 4-aminopyridine (50 μM) that block A-type K + currents. A selective NK 2 agonist, [βAla 8 ]-neurokinin A (4-10) (0.5 μM), mimicked the effects of SP. The effects of SP in C-R phasic neurons were fully reversed by an NK 2 receptor antagonist (MEN10376, 0.5 μM) but only partially by a protein kinase C (PKC) inhibitor (bisindolylmaleimide, 0.5 μM). An NK 3 selective agonist ([MePhe 7 ]-neurokinin B, 0.5 μM), an NK 1 selective agonist ([Sar 9 , Met 11 ]-substance P, 0.5 μM) or activation of PKC with phorbol 12, 13-dibutyrate (0.5 μM) did not change firing. Our data suggest that the excitability of C-R phasic afferent neurons is increased by activation of NK 2 receptors and intracellular signaling mediated only in part by PKC.

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“…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). On investigation of this response to H 2 S, they found that desensitization of capsaicin-sensitive primary afferent neurons by pretreatment with a high concentration of capsaicin, or pretreatment of tissues with a combination of tachykinin NK 1 and NK 2 receptor antagonists, abolished the response to H 2 S. These results provide definitive evidence that in the detrusor muscle the dominant effect of physiologically relevant concentrations of H 2 S involves stimulation of capsaicin-sensitive primary afferent neurons with consequent release of tachykinins, which in turn produce contractile responses of the detrusor muscle.…”

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confidence: 97%

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

Chahl

2004

British J Pharmacology

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Hydrogen sulphide (H 2 S) is a gas best known for its rotten egg smell. The toxic effects of high concentrations of H 2 S have been extensively investigated. It is known that H 2 S is generated in mammalian systems, but little is known of its effects in physiological concentrations. In the present issue of this journal, Patacchini et al. present evidence that H 2 S stimulates capsaicin-sensitive primary afferent neurons to release tachykinins in the rat urinary bladder. The possible significance of this finding is discussed in this commentary.

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Tachykinins and calcitonin gene-related peptide (CGRP) as co-transmitters released from peripheral endings of sensory nerves

Cited by 418 publications

References 1,044 publications

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

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

Neurokinins enhance excitability in capsaicin-responsive DRG neurons

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

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Tachykinins and calcitonin gene-related peptide (CGRP) as co-transmitters released from peripheral endings of sensory nerves

Cited by 418 publications

References 1,044 publications

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

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

Neurokinins enhance excitability in capsaicin-responsive DRG neurons

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

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

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