Regional peripheral and CNS hemodynamic effects of intrathecal administration of a substance P receptor agonist

Helke, Cinda J.; Phillips, E.T.; O'Neill, J Timothy

doi:10.1016/0165-1838(87)90086-5

Cited by 17 publications

(3 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The possible function of NK1 receptor-immunoreactive preganglionic neurons might be inferred from the responses to substance P and substance P agonists injected into the spinal cord. Intrathecal injections of SP or SP agonists at T2, T9-Tl0, L1 results in heart rate and blood pressure increases (Keeler et al, 1985;Yashpal et al, 1985;Riphagen et al, 1986;Hassessian et al, 1987Hassessian et al, , 1988Hassessian et al, , 1990Hassessian et al, , 1991Helke et al, 1987;Yashpal et al, 1987;Couture, 1988, 1989;Yashpal and Henry, 1993). The heart rate changes elicited by intrathecal substance P at the T9 level are greatly attenuated by cervical spinal section, suggesting the involvement of supraspinal pathways, rather than direct activation of sympathetic preganglionic neurons via NK1 receptors (Hassessian and Couture, 1989).…”

Section: Distribution Of Nk1 Receptor Immunoreactivity In Target-specmentioning

confidence: 99%

“…Substance P injected into the spinal cord has been shown to stimulate specific autonomic effects in the periphery (Keeler et al, 1985;Yashpal et al, 1985;Riphagen et al, 1986;Hassessian et al, 1987Hassessian et al, , 1988Hassessian et al, , 1990Hassessian et al, , 1991Helke et al, 1987;Yashpal et al, 1987;Couture, 1988, 1989;Yashpal and Henry, 1993), and intra-and extracellular recordings from sympathetic preganglionic neurons have confirmed that substance P has direct effects on preganglionic neurons (Gilbey et al, 1983;Backman and Henry, 1984;Dun and Mo, 1988;Cammack and Logan, 1996). However, these studies showed that not all preganglionic neurons respond to substance P, raising the possibility that substance P receptors are associated with only some specific functional groups of preganglionic neurons.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Distribution of immunoreactivity for the NK1 receptor on different subpopulations of sympathetic preganglionic neurons in the rat

Grković

Anderson

1996

J. Comp. Neurol.

View full text Add to dashboard Cite

The distribution of immunoreactivity to the receptor for substance P, the neurokinin 1 (NK1) receptor, was examined in preganglionic sympathetic neurons of the rat by using immunohistochemistry and retrograde neuronal tracing. About one-third of all sympathetic preganglionic neurons were NK1 receptor immunoreactive, and most of the NK1 receptor-immunoreactive neurons were also nitric oxide synthase immunoreactive. The proportions of sympathetic preganglionic neurons projecting to the superior and inferior mesenteric ganglia, adrenal gland, and lumbar sympathetic chain which were NK1 receptor-immunoreactive were determined. Most (89%) of the preganglionic neurons projecting to the adrenal glands were NK1 receptor immunoreactive. Few (17%) of the preganglionic neurons projecting to the L5 sympathetic chain ganglion were immunoreactive for the receptor, while preganglionic neurons projecting to the prevertebral ganglia were NK1 receptor immunoreactive at intermediate frequencies (61-64%). Thus, substance P acting on NK1 receptors is likely to be important in the preganglionic pathways to the adrenal medulla and viscera via the prevertebral ganglia, but is unlikely to be important in pathways to the lumbar sympathetic chain. The co-localisation of the NK1 receptor with the enzyme nitric oxide synthase was also examined. The majority of NK1 receptor-immunoreactive neurons were also nitric oxide synthase immunoreactive. Thus NK1 receptors occur on preganglionic neurons over many spinal segments and in a range of preganglionic pathways, as well as in a range of combinations with nitric oxide synthase. The heterogeneity of preganglionic neurons showing NK1 receptor immunoreactivity may reflect the involvement of NK1-mediated transmission in a variety of functional pathways, most notably the preganglionic projections to the adrenal medulla and to the viscera.

show abstract

Section: Distribution Of Nk1 Receptor Immunoreactivity In Target-specmentioning

confidence: 99%

mentioning

confidence: 99%

Distribution of immunoreactivity for the NK1 receptor on different subpopulations of sympathetic preganglionic neurons in the rat

Grković

Anderson

1996

J. Comp. Neurol.

View full text Add to dashboard Cite

show abstract

“…The autonomic effects of SP in the spinal cord are thought to be mediated by postsynaptic NKl receptors. Intrathecal administration of SP or a SP analog into the IML caused an increase in mean arterial pressure (Helke et al, 1987a;Jansen et al, 1991;Keeler et al, 1985), which was blocked by intrathecal injection of NK, antagonists (Helke et al, 1987b;Pham and Couture, 1993). These data indicate that activation of postsynaptic NK1 receptor has an excitatory effect on sympathetic preganglionic neurons in the IML.…”

Section: Discussionmentioning

confidence: 99%

Characterization of substance P release from the intermediate area of rat thoracic spinal cord

Yang

Thomas

Helke

1996

Synapse

View full text Add to dashboard Cite

Substance P (SP) nerve terminals innervate the intermediolateral cell column (IML) of the thoracic spinal cord, where SP coexists with serotonin (5-HT), neurokinin A (NKA) and thyrotropin-releasing hormone (TRH). Neither the depolarization-induced release of SP nor the presence of other neurochemicals in the regulation of SP release has been directly studied in this system. In the present study, basal and K(+)-stimulated release of SP from the microdissected intermediate area (including the IML, intercalated nucleus and central autonomic nucleus) of the rat thoracic spinal cord, and the regulation of SP release by presynaptic autoreceptors and by coexisting neurochemicals (5-HT, NKA and TRH) were studied using an in vitro superfusion system. Potassium evoked a concentration- and extracellular Ca(2+)-dependent release of SP. In rats pretreated with the serotoninergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), both SP content and the absolute amount of SP released were decreased. However, the fraction of the remaining tissue content of SP released by K+ depolarization was not changed subsequent to 5,7-DHT treatment. Moreover, 5-HT, 5-HT1B agonists (CGS-12066B and RU 24969) and a 5-HT3 agonist (2-methyl-5-HT) did not alter the K(+)-evoked release of SP. These data demonstrate that SP is released from the intermediate area of the rat thoracic spinal cord and some of the SP released comes from serotoninergic nerve terminals. Although 5-HT coexists with SP in the IML, neither endogenous 5-HT nor 5-HT receptor ligands appear to regulate the release of SP. Other colocalized neuropeptides (NKA and TRH) are not involved in the regulation of SP release because neither NKA, a NK2 agonist (GR 64349) nor a TRH analog (MK-771) changed the K(+)-evoked release of SP. A neurokinin-1 (NK1) antagonist (GR 82334) dose-dependently (10(-9)-10(-7) M) increased the K(+)-stimulated release of SP. These data suggest the presence of presynaptic inhibitory NK1 autoreceptors. Whereas, NK1 agonists, [GR 73632 (10(-9)-10(-6) M) and [Sar9, Met (O2)11]SP (10(-8)-10(-6) M)], increased the basal and K(+)-stimulated release of SP, the excitatory effects of GR 73632 were not blocked by the NK1 antagonist. Moreover, GR 73632 increased the efflus of SP to a greater extent in the absence of peptidase inhibitors. Thus, the effect of NK1 agonists on the release of SP may be related to an inhibition of peptide degradation rather than activation of NK1 autoreceptors.

show abstract

Role of neurotransmitters in the central regulation of the cardiovascular system

McCall

1990

Progress in Drug Research / Fortschritte Der Arzneimittelforschung / Progrès Des Recherches Pharmaceutiques

View full text Add to dashboard Cite

Regional peripheral and CNS hemodynamic effects of intrathecal administration of a substance P receptor agonist

Cited by 17 publications

References 25 publications

Distribution of immunoreactivity for the NK1 receptor on different subpopulations of sympathetic preganglionic neurons in the rat

Distribution of immunoreactivity for the NK1 receptor on different subpopulations of sympathetic preganglionic neurons in the rat

Characterization of substance P release from the intermediate area of rat thoracic spinal cord

Role of neurotransmitters in the central regulation of the cardiovascular system

Contact Info

Product

Resources

About