Presynaptic NK1 Receptor Activation by Substance P Suppresses EPSCs via Nitric Oxide Synthesis in the Rat Insular Cortex

The effects of activation and blockade of the neurokinin 1 (NK1) receptor in the rostral ventrolateral medulla (RVLM) on arterial blood pressure (ABP), splanchnic sympathetic nerve activity (sSNA), phrenic nerve activity, the somato-sympathetic reflex, baroreflex, and chemoreflex were studied in urethane-anesthetized and artificially ventilated Sprague-Dawley rats. Bilateral microinjection of either the stable substance P analog (pGlu5, MePhe8, Sar9)SP(5–11) (DiMe-SP) or the highly selective NK1 agonist [Sar9, Met (O2)11]SP into the RVLM resulted in an increase in ABP, sSNA, and heart rate and an abolition of phrenic nerve activity. The effects of [Sar9, Met (O2)11]SP were blocked by the selective nonpeptide NK1 receptor antagonist WIN 51708. NK1 receptor activation also dramatically attenuated the somato-sympathetic reflex elicited by tibial nerve stimulation, while leaving the baroreflex and chemoreflex unaffected. This effect was again blocked by WIN 51708. NK1 receptor antagonism in the RVLM, with WIN 51708 significantly attenuated the sympathoexcitatory response to hypoxia but had no effect on baseline respiratory function. Our findings suggest that substance P and the NK1 receptor play a significant role in the cardiorespiratory reflexes integrated within the RVLM.

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Altered vascular permeability responses to substance P in diabetic rats: Interactions with a nitric oxide synthesis inhibitor

European Journal of Pharmacology ◽

10.1016/0014-2999(93)90894-n ◽

1993 ◽

Vol 240 (2-3) ◽

pp. 163-168 ◽

Cited By ~ 7

Author(s):

Ronald Mathison ◽

Joseph S. Davison

Keyword(s):

Nitric Oxide ◽

Substance P ◽

Vascular Permeability ◽

Diabetic Rats ◽

Nitric Oxide Synthesis ◽

Synthesis Inhibitor

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An AMPA glutamatergic receptor activation-nitric oxide synthesis step signals transsynaptic apoptosis in limbic cortex

Neuropharmacology ◽

10.1016/j.neuropharm.2006.03.002 ◽

2006 ◽

Vol 51 (1) ◽

pp. 67-76 ◽

Cited By ~ 14

Author(s):

Yueping Zhou ◽

Lijun Zhou ◽

Haiming Chen ◽

Vassilis E. Koliatsos

Keyword(s):

Nitric Oxide ◽

Receptor Activation ◽

Limbic Cortex ◽

Nitric Oxide Synthesis

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Nitric oxide modulates renal sensory nerve fibers by mechanisms related to substance P receptor activation

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2001.281.1.r279 ◽

2001 ◽

Vol 281 (1) ◽

pp. R279-R290 ◽

Cited By ~ 33

Author(s):

Ulla C. Kopp ◽

Michael Z. Cicha ◽

Lori A. Smith ◽

Tomas Hökfelt

Keyword(s):

Nitric Oxide ◽

Substance P ◽

Sensory Nerve ◽

Receptor Activation ◽

Nerve Fibers ◽

Sensory Nerves ◽

Renal Nerve ◽

Inhibitory Neurotransmitter ◽

Pelvic Perfusion ◽

Pelvic Pressure

Nerve terminals containing neuronal nitric oxide synthase (nNOS) are localized in the renal pelvic wall where the sensory nerves containing substance P and calcitonin gene-related peptide (CGRP) are found. We examined whether nNOS is colocalized with substance P and CGRP. All renal pelvic nerve fibers that contained nNOS-like immunoreactivity (-LI) also contained substance P-LI and CGRP-LI. In anesthetized rats, renal pelvic perfusion with the nNOS inhibitor S-methyl-l-thiocitrulline (l-SMTC, 20 μM) prolonged the afferent renal nerve activity (ARNA) response to a 3-min period of increased renal pelvic pressure from 5 ± 0.4 to 21 ± 2 min ( P < 0.01, n = 14). The magnitude of the ARNA response was unaffected byl-SMTC. Similar effects were produced by N ω-nitro-l-arginine methyl ester (l-NAME) but not d-NAME. Increasing renal pelvic pressure produced similar increases in renal pelvic release of substance P before and during l-SMTC, from 5.9 ± 1.4 to 13.6 ± 4.2 pg/min before and from 4.9 ± to 12.6 ± 2.7 pg/min during l-SMTC. l-SMTC also prolonged the ARNA response to renal pelvic perfusion with substance P (3 μM) from 1.2 ± 0.2 to 5.6 ± 1.1 min ( P < 0.01, n = 9) without affecting the magnitude of the ARNA response. In conclusion: activation of NO may function as an inhibitory neurotransmitter regulating the activation of renal mechanosensory nerve fibers by mechanisms related to activation of substance P receptors.

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