Evidence that calcitonin gene-related peptide contributes to the capsaicin-induced relaxation of guinea pig cerebral arteries

Jansen, I.; Alafaci, Cetty; Uddman, Rolf; Edvinsson, Lars

doi:10.1016/0167-0115(90)90003-f

Cited by 47 publications

(26 citation statements)

References 33 publications

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“…Both of these tissues are richly innervated with capsaicin-sensitive sensory nerves, but the neurotransmitter systems responsible for the physiological readouts of nerve activation are different (Fujimori et al, 1990;Jansen et al, 1990;Franco-Cereceda, 1991;White et al, 1993;Lundberg, 1995;Zygmunt et al, 1999). We show that these two phenotypes of primary sensory nerve respond differently to the nonpungent N-acyl amines anandamide and olvanil.…”

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confidence: 93%

Mechanisms Underlying Tissue Selectivity of Anandamide and Other Vanilloid Receptor Agonists

et al. 2002

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Anandamide acts as a full vanilloid receptor agonist in many bioassay systems, but it is a weak activator of primary afferents in the airways. To address this discrepancy, we compared the effect of different vanilloid receptor agonists in isolated airways and mesenteric arteries of guinea pig using preparations containing different phenotypes of the capsaicin-sensitive sensory nerve. We found that anandamide is a powerful vasodilator of mesenteric arteries but a weak constrictor of main bronchi. These effects of anandamide are mediated by vanilloid receptors on primary afferents and do not involve cannabinoid receptors. Anandamide also contracts isolated lung strips, an effect caused by the hydrolysis of anandamide and subsequent formation of cyclooxygenase products. Although capsaicin is equally potent in bronchi and mesenteric arteries, anandamide, resiniferatoxin, and particularly olvanil are significantly less potent in bronchi. Competition experiments with the vanilloid receptor antagonist capsazepine did not provide evidence of vanilloid receptor heterogeneity. Arachidonoyl-5-methoxytryptamine (VDM13), an inhibitor of the anandamide membrane transporter, attenuates responses to olvanil and anandamide, but not capsaicin and resiniferatoxin, in mesenteric arteries. VDM13 did not affect responses to these agonists in bronchi, suggesting that the anandamide membrane transporter is absent in this phenotype of the sensory nerve. Computer simulations using an operational model of agonism were consistent, with differences in intrinsic efficacy and receptor content being responsible for the remaining differences in agonist potency between the tissues. This study describes differences between vanilloid receptor agonists regarding tissue selectivity and provides a conceptual framework for developing tissue-selective vanilloid receptor agonists devoid of bronchoconstrictor activity.

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confidence: 93%

Mechanisms Underlying Tissue Selectivity of Anandamide and Other Vanilloid Receptor Agonists

et al. 2002

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“…The majority of these nerve cells stain positive for one or more of the neuropeptides substance P (SP), calcitonin gene related peptide (CGRP), and neurokinin A (NK-A) (Edvinsson et al, 1981). Release of neuropeptides from peripheral terminals was demonstrated after electrical stimulation of trigeminal nerve fibers (Goadsby et al, 1988) or capsaicin application to cerebral blood vessels (Duckles and Buck, 1982;Jansen et al, 1990). While most studies of peptidergic innervation of the meninges were focussed on fibers supplying the vasculature, recent anatomical studies have revealed the presence of nerve fibers immunoreactive for several neuropeptides also within the leptomeninx, including fibers positive for SP and CGRP terminating close to the subarachnoid space (Fricke et al, 1997).…”

Section: Anatomical Considerationsmentioning

confidence: 98%

The trigeminovascular system in bacterial meningitis

Hoffmann¹,

Dirnagl²,

Weber³

2001

Microscopy Res & Technique

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Headache as a cardinal symptom of acute meningitis reflects activation of trigeminal afferents from the meninges. With their perivascular endings, these fibers form the so-called trigeminovascular system (TVS), which releases proinflammatory neuropeptides upon nociceptive stimulation. In the present article, we review a role of the TVS in enhancing the early inflammatory response of bacterial meningitis. Furthermore, we discuss inhibition of neuropeptide release from the TVS using 5HT(1B/D) agonists as a potential new anti-inflammatory treatment strategy for early bacterial meningitis.

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“…In mammals, however, there have been pharmacological reports stating that SP acts as a nonadrenergic and noncholinergic vasodilator in the pial arteries that depend on the vascular endothelium, and also as a transmitter of nociceptive and other sensory information from blood vessels to the brain [8,11]. It has al so bee n doc ume nte d t ha t C GR P c a use s s trong nonadrenergic and noncholinergic vasodilatation through its direct action on vascular smooth muscles, restores vessel diameter after vasoconstriction by reflex response, and potentiates the vascular permeability induced by SP [6,7,15,21,22]. Accordingly, it can be inferred that SP-and CGRP-IR nerves supplying the quail cerebral arteries may be involved in the direct and indirect vasocontrolling actions regulating the cerebral blood flow.…”

Section: Discussionmentioning

confidence: 99%

“…Of the four distinct types of cerebrovascular peptidergic nerves, SP-and CGRPimmunoreactive (IR) nerves are almost equal in density, a n d p r o v o k e a s i g n i f i c a n t d e p l e t i o n o f t h i s immunoreactivity after capsaicin treatment, being indicative of the primary sensory origin [8,15]. Doubleimmunostaining has confirmed that SP and CGRP coexist in the same cerebral perivascular axons [9,20,29,31].…”

mentioning

confidence: 99%

Innervation Pattern of Substance P- and Calcitonin Gene-related Peptide-Immunoreactive Nerves of the Cerebral Arteries in the Quail

Kusaba¹,

Andō

Fujihara

2000

The Journal of Veterinary Medical Science

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ABSTRACT. The pattern of cerebrovascular substance P (SP)-and calcitonin gene-related peptide (CGRP)-immunoreactive (IR) innervation was investigated in the quail. SP-and CGRP-IR nerves were relatively a few in the rostral part of the anterior circulation, and very scanty or lacking in its caudal part and the whole of the posterior circulation. A significant finding was that the anterior circulation in the majority of individuals is furnished with a varying proportion of SP-IR nerves with or without CGRP immunoreactivity. There was a good correlation in the expression of CGRP immunoreactivity between SP-IR cells in the ophthalmic division of the trigeminal ganglion and SP-IR nerves supplying the major cerebral arteries. In the quail, SP-and CGRP-IR fiber bundles are usually present in the internal ethmoidal artery (IEA). From these and other findings, it is most probable that cerebral perivascular SP-and CGRP-IR nerves are mainly derived from the same categories of neurons in the primary sensory ganglion via the IEA. The close association of varicose SP-IR axons to the nerve cells in the pial arteries suggests that these intrinsic neurons may play some vasocontrolling roles through the modulatory effect of their pericellular SP-IR axons.-KEY WORDS: calcitonin gene-related peptide, cerebral artery, innervation, quail, substance P.The mammalian cerebral vascular bed is known to be supplied by nerves containing various types of bioactive peptides, such as vasoactive intestinal polypeptide, neuropeptide Y, substance P (SP) and calcitonin-gene related peptide (CGRP) [10,28]. Of the four distinct types of cerebrovascular peptidergic nerves, SP-and CGRPimmunoreactive (IR) nerves are almost equal in density, a n d p r o v o k e a s i g n i f i c a n t d e p l e t i o n o f t h i s immunoreactivity after capsaicin treatment, being indicative of the primary sensory origin [8,15]. Doubleimmunostaining has confirmed that SP and CGRP coexist in the same cerebral perivascular axons [9,20,29,31]. Both the origin and the pathway of cerebrovascular SP-and CGRP-IR innervations have also been corroborated by ganglionectomy and/or a retrograde tracing technique [24,27,30,31].The angioarchitecture of the cerebral arterial system in avian species is essentially divergent from that of mammal and other vertebrate groups [4,5,16]. Furthermore, our previous histochemical studies revealed that the density of cerebral perivascular acetylcholinesterase (AChE) nerves varied markedly between the quail and the duck, despite the very rich supply of noradrenergic nerves [3,4]. This is clearly different from the general mammalian pattern in that the major cerebral arteries are supplied by AChE and noradrenergic nerves with approximately the same density [32]. The above two studies [3,4] have also demonstrated the occurrence of AChE nerve cells in the major cerebral arteries which has not been reported in mammals. To determine a further explication of neuronal influence on the avian cerebral circulation, we investigated the overall distribution of...

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Evidence that calcitonin gene-related peptide contributes to the capsaicin-induced relaxation of guinea pig cerebral arteries

Cited by 47 publications

References 33 publications

Mechanisms Underlying Tissue Selectivity of Anandamide and Other Vanilloid Receptor Agonists

Mechanisms Underlying Tissue Selectivity of Anandamide and Other Vanilloid Receptor Agonists

The trigeminovascular system in bacterial meningitis

Innervation Pattern of Substance P- and Calcitonin Gene-related Peptide-Immunoreactive Nerves of the Cerebral Arteries in the Quail

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