Serotonin Neurons Project to Small Blood Vessels in the Brain

Reinhard, John F.; Liebmann, James; Schlosberg, Arthur J.; Moskowitz, Michael A.

doi:10.1126/science.482930

Cited by 196 publications

(56 citation statements)

References 38 publications

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“…In fact there are some data to support this suggestion [19,44,160] showing close association between intracerebral nerve fibers and cerebral blood vessels. This has been examined at depth subsequently revealing a direct neurogenic control by intrinsic serotonergic (5-HT) neurons on the cerebral microvascular bed [28].There exist close association between the 5-HT neurons and microarterioles, capillaries and perivascular astrocytes; this is more apparent in regions where manipulation of the intrinsic 5-HT neurons elicits uncoupling between flow and metabolism [28,29] In patients with migraine without aura, the situation is somewhat more intricate [199].…”

Section: IImentioning

confidence: 89%

Neurobiology in primary headaches

Edvinsson

Uddman

2005

Brain Research Reviews

212

209

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Section: IImentioning

confidence: 89%

Neurobiology in primary headaches

Edvinsson

Uddman

2005

Brain Research Reviews

212

209

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“…In cerebral arteries, noradrenaline (NA, IWAYAMA et al, 1970), acetylcholine (ACh, LEE et al, 1978), 5-hydroxytryptamine (5-HT, REINHARD et al, 1979), adenosine triphosphate (ATP, MURAMATSU et al,1981), or substance P (EDVINSSON et al, 1981) have been considered as the putative transmitter substances of the perivascular nerves. Involvement of sympathetic nerve in regulation of the cerebral vascular tone has been receiving increased attention (PURVES, 1978), because this nerve regulates smooth muscle tone in the majority of peripheral vasculatures (BEVAN et al, 1980).…”

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confidence: 99%

Non-neural electrical responses of smooth muscle cells of the rabbit basilar artery to electrical field stimulation.

Nagao

Suzuki

1987

Jpn.J.Physiol

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In smooth muscle cells of the rabbit basilar artery, field stimulation evoked a depolarizing response which consisted of a fast (1-3 s duration) and a following slow (1-4min duration) component. The amplitude of these responses increased in an intensity-dependent manner and, when exceeding 10-15 mV, a spike potential was generated. During generation of the slow depolarization, ionic conductances of the membrane were increased. When outward current pulses with long duration (2-3 s) were applied to the smooth muscle using the partition stimulating method, electrotonic potentials and spike potentials were generated. The cessation of the current pulse caused repolarization of the membrane with time constant of 250-350 ms. The depolarizing responses were resistant to tetrodotoxin, sympathetic transmission blocking agents (guanethidine, bretylium, or 6-hydroxydopamine treatment), receptor antagonists for 5-hydroxytryptamine (methysergide), dopamine (haloperidol), ACh (atropine), noradrenaline (phentolamine), ATP (a,f-mATP) or histamine (mepyramine), blockade of synthesis of prostaglandins or thromboxane A2 (indomethacin) or high Mgt + j low Cat + solution. Smooth muscle cell membrane of the basilar artery was depolarized by 5-hydroxytryptamine (above 0.1 µM) or histamine (above 10 µM) but not by ACh (up to 100 µM) or noradrenaline (up to 10 µM). The depolarization induced by 5-hydroxytryptamine or histamine was antagonized by methysergide or mepyramine, respectively. Denervation of the vessel by storing in a cold condition (4°C) decreased but did not abolish the depolarizing response. The decrease in amplitude of the depolarizing response during cold storage was attributed to associated depolarization of the smooth muscle membrane. Internal perfusion of the vessel with distilled water abolished generation of the depolarizing response, and this procedure also abolished the endothelium-dependent relaxation induced by ACh during the potassium contraction. The results suggest that the depolarizing response evoked by field stimulation is generated by substances released from nonneural components, possibly from the endothelial cells.

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“…Interestingly, an innervation of intraparenchymal blood vessels by 5-HT has been demonstrated in the brainstem (Chan-Palay, 1976;Di Carlo, 1977;Kapadia & de Lanerolle, 1984), an observation which could be consistent with a role for 5-HT in the control of cerebral perfusion and, particularly in caudal brain areas. This hypothesis might be further supported by the fact that the perivascular 5-hydroxytryptaminergic innervation originates from the mesencephalic raphe nuclei of the brain stem (Reinhard et al, 1979;Edvinsson et al, 1983a;Scatton et al, 1985). However, it has been shown that part of the characterized 5-hydroxytryptaminergic innervation might be due to the capacity of sympathetic perivascular nerves to accumulate and release 5-hydroxytryptamine (Verbeuren et al, 1983;Levitt & Duckles, 1986;Saito & Lee, 1987).…”

Section: -Hydroxytryptaminementioning

confidence: 99%

Heterogeneous vasomotor responses of anatomically distinct feline cerebral arteries

Hamel

Edvinsson

MacKenzie

1988

British J Pharmacology

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1 The vasomotor reactivity to a number of neurotransmitters and blood-borne substances was evaluated in several anatomically distinct arteries of the cat cerebral circulation. Few regional differences were observed in their vasoconstrictor responses to noradrenaline, dopamine, 5-hydroxytryptamine and prostaglandin F2a. Only the anterior cerebral artery reacted strongly to all vasoconstrictor agents. 2 Adenosine, acetylcholine and histamine induced pronounced relaxation in the vast majority of the major cerebral arteries. The relaxation elicited by adenosine showed a slight degree of heterogeneity between the arteries and the overall response accounted for 81 + 6% of the pharmacologically-induced tone. On the other hand, the dilatation induced by acetylcholine and histamine varied as a function of the anatomical localization of the cerebral arteries. The acetylcholine-induced vasodilatation was significantly more pronounced in the middle cerebral, anterior communicating and anterior cerebellar arteries, with respective responses of 72, 66 and 83% of the induced tone as compared to 43% in the other vessels. However, all arteries were equally sensitive to acetylcholine with an overall mean pD2 value of 7.47 + 0.06. The most heterogeneous results were obtained with histamine and applied both to the magnitude of the maximal response and the sensitivity of the various arteries to this amine. The intensity of the relaxation varied from 20% (anterior communicating artery) to 118% (posterior cerebellar artery). 3 Among the neuropeptides studied, substance P and bradykinin were considerably less potent than vasoactive intestinal peptide on all the cerebral arteries. The least responsive vessel to bradykinin was the anterior cerebral artery with a maximal response of 22 + 5% of the induced-tone and a pD2 value of 7.56 + 0.24. All vessels responded weakly to substance P and those from the vertebrobasilar circulation were significantly less sensitive to this neuropeptide with pD2 values around 8.07 as compared to 9.82 in the more rostral arteries. Although all vessels were equally sensitive to vasoactive intestinal peptide, the dilator responses were significantly less pronounced in the middle cerebral and basilar arteries (maximal response of 86 + 5% and 69 + 6% of the induced-tone, respectively, as compared to 110 + 9% in the other vessels). 4 The vertebrobasilar arteries were as reactive, if not more reactive, to vasoconstrictors than the vessels originating from the carotid circulation. In contrast, the dilator responses were less marked in most caudal arteries. Such dichotomies may be important in the regulation of local cerebral blood flow. 5 The results emphasize the considerable heterogeneity in the vasomotor responses to a given substance among the various cerebral arteries. Further, they suggest the presence of multiple receptor populations which mediate opposite effects and which are distributed in different proportions among the cephalic arteries.

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Serotonin Neurons Project to Small Blood Vessels in the Brain

Cited by 196 publications

References 38 publications

Neurobiology in primary headaches

Neurobiology in primary headaches

Non-neural electrical responses of smooth muscle cells of the rabbit basilar artery to electrical field stimulation.

Heterogeneous vasomotor responses of anatomically distinct feline cerebral arteries

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