Dynorphin B-Containing Perivascular Axons and Sensory Neurotransmitter Mechanisms in Brain Blood Vessels

Cephalalgia ◽  
1986 ◽  
Vol 6 (2) ◽  
pp. 81-86 ◽  
Author(s):  
Michael A Moskowitz ◽  
Lisa R Brezina ◽  
Christine Kuo
Keyword(s):  
Substance P ◽  
Blood Vessels ◽  
Ganglion Cells ◽  
Cerebral Arteries ◽  
Nerve Fibers ◽  
Sensory Axons ◽  
Middle Cerebral Arteries ◽  
Dorsal Root Ganglion Cells ◽  
Opiate Analgesic

This is the first report demonstrating the existence of opiate-containing nerve fibers surrounding brain blood vessels. Dynorphin B, a tridecapeptide and potent opiate analgesic, was visualized by immunohistochemistry in guinea pig cerebral arteries comprising the circle of Willis and was measured by radioimmunoassay in canine middle cerebral arteries. This peptide, reportedly present in dorsal root ganglion cells, was observed by others to decrease the depolarization-induced release of substance P from primary sensory axons and, by so doing, to retard the development of neurogenic inflammation in target tissues. Consistent with an indirect action of dynorphin B, this peptide did not relax precontracted canine middle cerebral or basilar artery segments when added in vitro, nor did it modulate receptor-mediated relaxation on the addition of substance P. The presence of opiate-containing axons in or near trigeminovascular nerve fibers suggests novel mechanisms related to the modulation of pain possibly emanating from cerebral vessels.

scholarly journals Nerve Fibers Containing Neuropeptide Y in the Cerebrovascular Bed: Immunocytochemistry, Radioimmunoassay, and Vasomotor Effects

1987 ◽  
Vol 7 (1) ◽  
pp. 45-57 ◽  
Author(s):  
L. Edvinsson ◽  
J. R. Copeland ◽  
P. C. Emson ◽  
J. McCulloch ◽  
R. Uddman
Keyword(s):  
Neuropeptide Y ◽  
Blood Vessels ◽  
Superior Cervical Ganglion ◽  
Cerebral Arteries ◽  
Nerve Fibers ◽  
Calcium Entry Blocker ◽  
Cervical Ganglion ◽  
Prostaglandin F ◽  
6 Hydroxydopamine

Perivascular nerve fibers containing neuropeptide Y (NPY)-like immunoreactivity were identified around cerebral blood vessels of human, cat, guinea pig, rat, and mouse. The major cerebral arteries were invested by dense plexuses; veins, small arteries, and arterioles were accompanied by few fibers. Removal of the superior cervical ganglion resulted in a reduction of NPY-like material in pial vessels and dura mater. Pretreatment with 6-hydroxydopamine or reserpine reduced the number of visible NPY fibers and the concentration of NPY in rat cerebral vessels. Sequential immuno-staining with antibodies toward dopamine-β-hydroxylase (DBH) (an enzyme involved in the synthesis of noradrenaline) and NPY revealed an identical localization of DBH and NPY in nerve cell bodies in the superior cervical ganglion and in perivascular fibers of pial blood vessels, suggesting their coexistence. Administration of NPY in vitro resulted in concentration-dependent contractions that were not modified by a sympathectomy. The contractions induced by noradrenaline, 5-hydroxytryptamine, and prostaglandin F2α and the dilator responses to calcitonin gene-related peptide were not modified by NPY in rat cerebral arteries. However, the constrictor response to NPY was reduced by 70% in the presence of the calcium entry blocker nifedipine, and abolished following incubation in a calcium-free buffer. These data suggest an interaction of NPY at a postsynaptic site, which for induction of contraction may open calcium channels in the sarcolemma of cerebral arteries.

scholarly journals Calcitonin Gene-Related Peptide and Cerebral Blood Vessels: Distribution and Vasomotor Effects

1987 ◽  
Vol 7 (6) ◽  
pp. 720-728 ◽  
Author(s):  
L. Edvinsson ◽  
R. Ekman ◽  
I. Jansen ◽  
J. McCulloch ◽  
R. Uddman
Keyword(s):  
Substance P ◽  
Guinea Pig ◽  
Blood Vessels ◽  
Mammalian Species ◽  
Cerebral Arteries ◽  
Nerve Fibers ◽  
Neurokinin A ◽  
Cerebral Blood Vessels ◽  
Calcitonin Gene ◽  
Basilar Arteries

The innervation of cerebral blood vessels by nerve fibers containing calcitonin gene-related peptide (CGRP) and the vasomotor effects of this peptide are described for a number of different mammalian species. CGRP-immunoreactive nerve fibers were present in the adventitia of cerebral arteries in all species examined (guinea pig, cat, rabbit, rat, and mouse). Numerous perikarya containing CGRP immunoreactivity are demonstrable in the trigeminal ganglion of all species. In the cerebral perivascular nerve fibers and in trigeminal perikarya, CGRP is often colocalized with substance P and neurokinin A. Marked interspecies differences exist both in the density of CGRP-immunoreactive nerve fibers and in the cerebrovascular levels measured with radioimmunoassay. The highest concentrations were observed in cerebral vessels from guinea pigs, the lowest concentration in rabbit vessels, and intermediate levels in the feline and human cerebral vasculature. CGRP is a potent dilator of cerebral arteries in all species examined (human pial, feline middle cerebral, rabbit, guinea pig and rat basilar arteries). The concentration of CGRP eliciting half-maximal responses ranged from 0.4 n M (human pial artery) to 3 n M (rat and rabbit basilar arteries). Pretreatment of cerebral arteries with low concentrations of either substance P (0.1 n M) or neurokinin A (3 n M) attenuated slightly the CGRP-induced relaxations of guinea pig basilar arteries. Calcitonin was found to be a very weak dilator of cerebral arteries from human and guinea pig. Thus, cardiovascular nerve fibers containing CGRP appear to be present in all mammalian species (although to varying degrees) and CGRP is invariably a potent dilator of the cerebral arteries for all species.

scholarly journals Contractile and Endothelium-Dependent Dilatory Responses of Cerebral Arteries at Various Extracellular Magnesium Concentrations

1991 ◽  
Vol 11 (1) ◽  
pp. 161-164 ◽  
Author(s):  
Mária Faragó ◽  
Csaba Szabó ◽  
Eörs Dóra ◽  
Ildikó Horváth ◽  
Arisztid G. B. Kovách
Keyword(s):  
Smooth Muscle ◽  
Vascular Reactivity ◽  
Calcium Influx ◽  
Cerebral Arteries ◽  
Inhibitory Effect ◽  
Contractile Responses ◽  
Middle Cerebral Arteries ◽  
The Right ◽  
Endothelial Receptor

To clarify the effect of extracellular magnesium (Mg2+) on the vascular reactivity of feline isolated middle cerebral arteries, the effects of slight alterations in the Mg2+ concentration on the contractile and endothelium-dependent dilatory responses were investigated in vitro. The contractions, induced by 10−8-10−5 M norepinephrine, were significantly potentiated at low Mg2+ (0.8 m M v. the normal, 1.2 m M). High (1.6 and 2.0 m M) Mg2+ exhibited an inhibitory effect on the contractile responses. No significant changes, however, in the EC50 values for norepinephrine were found. The endothelium-dependent relaxations induced by 108–10−5 M acetylcholine were inhibited by high (1.6 and 2.0 m M) Mg2+. Lowering of the Mg2+ concentration to 0.8 m M or total withdrawal of this ion from the medium failed to alter the dilatory potency of acetylcholine. The changes in the dilatory responses also shifted the EC50 values for acetylcholine to the right. The present results show that the contractile responses of the cerebral arteries are extremely susceptible to the changes of Mg2+ concentrations. In response to contractile and endothelium-dependent dilatory agonists, Mg2+ probably affects both the calcium influx into the endothelial and smooth muscle cells as well as the binding of acetylcholine to its endothelial receptor. Since Mg2+ deficiency might facilitate the contractile but not the endothelium-dependent relaxant responses, the present study supports a role for Mg2+ deficiency in the development of the cerebral vasospasm.

In vitro analysis of interactions between sensory neurons and skin: evidence for selective innervation of dermis and epidermis

Development ◽  
1985 ◽  
Vol 86 (1) ◽  
pp. 53-70
Author(s):  
J.-M. Verna
Keyword(s):  
Ganglion Cells ◽  
Neurite Growth ◽  
Epidermal Cells ◽  
Serum Free Medium ◽  
Diffusible Factor ◽  
Vitro Analysis ◽  
Dermal Cells ◽  
Dorsal Root Ganglion Cells ◽  
In Vitro Analysis

Axons from dorsal root ganglion cells cultured in a serum-free medium on poly-L-lysine or collagen substrates interact differently with dermis and epidermis. The orientation of neurite growth is not changed by encountering mesenchymal cells migrating from the outgrowth zone of a dermal explant, and neurites form close membrane associations with some dermal cells; in contrast, neurites strongly avoid epidermis and deviate around the edge of an epidermal explant. When cultures are grown on polylysine this avoidance behaviour occurs at a distance from the epidermis. It is suppressed in the presence of necrotic epidermal cells. We suggest that this avoidance is due to epidermal diffusible factor(s) which bind preferentially to polylysine. The possibility of an absence of specific recognition cues between neurites and epidermal cells is discussed.

Effects of ischemia and myogenic activity on active and passive mechanical properties of rat cerebral arteries

2002 ◽  
Vol 283 (6) ◽  
pp. H2268-H2275 ◽  
Author(s):  
Rebecca J. Coulson ◽  
Naomi C. Chesler ◽  
Lisa Vitullo ◽  
Marilyn J. Cipolla
Keyword(s):  
Contractile Activity ◽  
Cerebral Arteries ◽  
Biomechanical Properties ◽  
Short Term ◽  
Mechanical Stiffness ◽  
Middle Cerebral Arteries ◽  
Male Wistar Rats ◽  
Myogenic Activity ◽  
Activity Dependent

Passive (papaverine induced) and active (spontaneous pressure induced) biomechanical properties of ischemic and nonischemic rat middle cerebral arteries (MCAs) were studied under pressurized conditions in vitro. Ischemic (1 h of occlusion), contralateral, and sham-operated control MCAs were isolated from male Wistar rats ( n = 22) and pressurized using an arteriograph system that allowed control of transmural pressure (TMP) and measurement of lumen diameter and wall thickness. Three mechanical stiffness parameters were computed: overall passive stiffness (β), pressure-dependent modulus changes ( E inc,p), and smooth muscle cell (SMC) activity-dependent changes ( E inc,a). The β-value for ischemic vessels was increased compared with sham vessels (13.9 ± 1.7 vs. 9.1 ± 1.4, P < 0.05), indicating possible short-term remodeling due to ischemia. E inc,p increased with pressure in the passive vessels ( P < 0.05) but remained relatively constant in the active vessels for all vessel types, indicating that pressure-induced SMC contractile activity (i.e., myogenic reactivity) in cerebral arteries leads to the maintenance of a constant elastic modulus within the autoregulatory pressure range. E inc,a increased with pressure for all conditions, signifying that changes in stiffness are influenced by SMC activity and vascular tone.

scholarly journals Amylin: Localization, Effects on Cerebral Arteries and on Local Cerebral Blood Flow in the Cat

2001 ◽  
Vol 1 ◽  
pp. 168-180 ◽  
Author(s):  
Lars Edvinsson ◽  
Peter J. Goadsby ◽  
Rolf Uddman
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Blood Vessels ◽  
Cerebral Arteries ◽  
In Vivo Studies ◽  
Cerebral Blood Vessels ◽  
Local Cerebral Blood Flow ◽  
Doppler Flowmetry

Amylin and adrenomedullin are two peptides structurally related to calcitonin gene-related peptide (CGRP). We studied the occurrence of amylin in trigeminal ganglia and cerebral blood vessels of the cat with immunocytochemistry and evaluated the role of amylin and adrenomedullin in the cerebral circulation by in vitro and in vivo pharmacology. Immunocytochemistry revealed that numerous nerve cell bodies in the trigeminal ganglion contained CGRP immunoreactivity (-ir); some of these also expressed amylin-ir but none adrenomedullin-ir. There were numerous nerve fibres surrounding cerebral blood vessels that contained CGRP-ir. Occasional fibres contained amylin-ir while we observed no adrenomedullin-ir in the vessel walls. With RT-PCR and Real-Time�PCR we revealed the presence of mRNA for calcitonin receptor-like receptor (CLRL) and receptor-activity-modifying proteins (RAMPs) in cat cerebral arteries. In vitro studies revealed that amylin, adrenomedullin, and CGRP relaxed ring segments of the cat middle cerebral artery. CGRP and amylin caused concentration-dependent relaxations at low concentrations of PGF2a-precontracted segment (with or without endothelium) whereas only at high concentration did adrenomedullin cause relaxation. CGRP8-37 blocked the CGRP and amylin induced relaxations in a parallel fashion. In vivo studies of amylin, adrenomedullin, and CGRP showed a brisk reproducible increase in local cerebral blood flow as examined using laser Doppler flowmetry applied to the cerebral cortex of the a-chloralose�anesthetized cat. The responses to amylin and CGRP were blocked by CGRP8-37. The studies suggest that there is a functional sub-set of amylin-containing trigeminal neurons which probably act via CGRP receptors.

scholarly journals Immunohistochemical evidence for the presence of a vasoactive intestinal peptide, neuropeptide Y and substance P in rat adrenal medulla after heat stress

2012 ◽  
Vol 64 (1) ◽  
pp. 7-13
Author(s):  
Dragana Petrovic-Kosanovic ◽  
Vesna Koko
Keyword(s):  
Heat Stress ◽  
Substance P ◽  
Neuropeptide Y ◽  
Vasoactive Intestinal Peptide ◽  
Adrenal Medulla ◽  
Chromaffin Cells ◽  
Ganglion Cells ◽  
Nerve Fibers ◽  
Acute Heat Stress ◽  
Immunohistochemical Evidence

Immunohistochemistry revealed the presence of VIP-, NPY- and SP-immunoreactivity in the rat adrenal medulla. VIP- and NPY-immunoreactivity was detected in chromaffin and ganglion cells and in nerve fibers, but SP-immunoreactivity was found only in chromaffin cells. After acute heat stress, VIP- and NPY- immunoreactivities in cells and nerve fibers were reduced, probably as a result of the release of these peptides with catecholamines. The absence of SP-immunoreactive ganglion cells in the adrenal medulla suggests that the SP-immunoreactive nerve fibers are extrinsic in origin.

Bullfrog dorsal root ganglion cells having tetrodotoxin-resistant spikes are endowed with nicotinic receptors

1989 ◽  
Vol 62 (3) ◽  
pp. 657-664 ◽  
Author(s):  
K. Morita ◽  
Y. Katayama
Keyword(s):  
Dorsal Root Ganglion ◽  
Conduction Velocity ◽  
Dorsal Root ◽  
Time Course ◽  
Ganglion Cells ◽  
Reversal Potential ◽  
Membrane Resistance ◽  
Fast Response ◽  
Dorsal Root Ganglion Cells

1. Intracellular recordings were made from bullfrog dorsal root ganglion (DRG) neurons in vitro. They were divided into three types, As, Ar, and C, according to their conduction velocity and their sensitivity to tetrodotoxin [TTX (less than or equal to 1 microM)]; an As neuron had a fast conduction velocity (13-50 m/s, mean = 31 m/s, n = 73) and TTX-sensitive sodium soma spikes: an Ar neuron showed a fast conduction velocity (4-28 m/s, mean = 14 m/s, n = 52) and TTX-resistant sodium soma spikes; and a C neuron had a slow conduction velocity (0.16-0.8 m/s, mean = 0.4 m/s, n = 49) and TTX-resistant sodium-calcium soma spikes. 2. Superfusion of acetylcholine [ACh (0.3 microM-1 mM)] produced a fast depolarization in 70% of Ar and in 50% of C neurons. No As neuron showed a fast depolarization in response to ACh. The ACh-induced fast response persisted in calcium-free or TTX-containing solutions. 3. The response in both Ar and C neurons was similar except in time course; the response was always more rapid in C than in Ar neurons. The response was always associated with a decreased membrane resistance and reversed in polarity at about -30 mV. The reversal potential varied with both sodium and potassium concentrations of the superfusing solutions. 4. Nicotine, (+)-tubocurarine [(+)-TC], and hexamethonium reversibly blocked the ACh fast response.(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of development and chronic hypoxia on NE release from adrenergic nerves in sheep arteries

1999 ◽  
Vol 276 (3) ◽  
pp. R799-R808 ◽  
Author(s):  
John Buchholz ◽  
Kim Edwards-Teunissen ◽  
Sue P. Duckles
Keyword(s):  
Chronic Hypoxia ◽  
Cerebral Arteries ◽  
Sensory Nerves ◽  
Adrenergic Nerves ◽  
Facial Artery ◽  
Norepinephrine Release ◽  
Differential Adaptation ◽  
Middle Cerebral Arteries ◽  
The Face

To examine effects of development and chronic high-altitude hypoxia on sympathetic nerve function in sheep, norepinephrine release was measured in vitro from middle cerebral and facial arteries. Capsaicin was used to test the role of capsaicin-sensitive sensory nerves; norepinephrine release was not altered by capsaicin treatment. N ω-nitro-l-arginine methyl ester (l-NAME), an inhibitor of NO synthase, decreased stimulation-evoked norepinephrine release in middle cerebral arteries from normoxic sheep with no effect in hypoxic arteries or facial arteries. Thus NO-releasing nerves augmented norepinephrine release. Furthermore, the function of NO-releasing nerves declined after chronic hypoxia. Despite loss of the augmenting effects of NO, stimulation-evoked fractional norepinephrine release was unchanged after chronic hypoxia, suggesting that middle cerebral arteries adapt to hypoxia by increasing stimulation-evoked norepinephrine release. In fetal facial arteries, chronic hypoxia resulted in a decline in stimulation-evoked norepinephrine release, but there was an increase in the adult facial artery. In the adult, adaptation to chronic hypoxia is similar in both cerebral and facial arteries. However, differential adaptation in fetal adrenergic nerves may reflect differences in fetal redistribution of blood flow in the face of chronic hypoxia but could also possibly contribute to increased incidence of fetal morbidity.

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