Pituitary adenylate cyclase activating peptide is a sensory neuropeptide: Immunocytochemical and immunochemical evidence

Möller, Kristian; Zhang, Y.-Z.; Håkanson, R.; Luts, A.; Sjölund, Bengt H.; Uddman, Rolf; Sundler, F.

doi:10.1016/0306-4522(93)90018-b

Cited by 240 publications

(140 citation statements)

References 19 publications

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“…On the other hand, the rich existence of CGRP in the nasal mucosa has been demonstrated by radioimmunoassay and by immunohistochemistry in several species, including humans (SILVERMAN and KRUGER, 1989;STJARNE et al, 1989;FINGER et al, 1990;MOLLER et al, 1993). There is general agreement that unmyelinated sensory fibers in the peripheral organs usually contain CGRP as well as SP; the former was noted to be more extensively and intensely immunostained in sensory nerves in various tissues, including nasal mucosa (LUNDBERG and HOKFELT, 1986).…”

Section: Discussionmentioning

confidence: 99%

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Intraepithelial Nerve Fibers in the Nasal Mucosa of the Rat with Special Reference to the Localization of CGRP, VIP and Nitric Oxide (NO).

Lee

Iwanaga

Fujita

1995

Archives of Histology and Cytology

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Summary. Previous studies have demonstrated that the epithelium of the respiratory portion of rat nasal mucosa is amply supplied by nerve fibers with immunoreactivities for calcitonin gene-related peptide (CGRP) and substance P (SP), these fibers most likely acting as sensory mediators in the mucosa. The present study demonstrates that some intraepithelial fibers contain a VIP-immunoreactivity whose occurrence in these nerves has previously been neglected. The present study further aims to confirm the occurrence of NO-producing intraepithelial nerve fibers in the rat nasal mucosa and to examine its colocalization with CGRP and with VIP.Double staining methods were used to evaluate the colocalization of NADPH-diaphorase reactivity and CGRP-or VIP-immunoreactivity.The reactivity for NADPH-diaphorase and that for CGRP coexisted in only a small part, if any, of the nerve fibers distributed at the basal portion of the epithelium. In the perpendicularly and obliquely oriented transepithelial nerve fibers, both reactivities were clearly demonstrated to be separated in different fibers.VIP immunoreactivity was also present in a part of the intraepithelial nerve fibers of the nasal mucosa, and their entire population was shown to be positive for NADPH-diaphorase.The NADPH-diaphorase-positive reaction was displayed in only a small population of neurons in the trigeminal ganglion, whereas it was seen in numerous neurons in sphenopalatine ganglion, being colocalized with VIP.

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Section: Discussionmentioning

confidence: 99%

“…Hence, CGRP has been described as a major mediator of the trigeminal chemoreaction and is favored as the immunohistochemical marker for the sensory nerves of the nasal mucosa (SILVERMAN and KRUGER, 1989;FINGER et al, 1990;MOLLER et al, 1993).…”

mentioning

confidence: 99%

Intraepithelial Nerve Fibers in the Nasal Mucosa of the Rat with Special Reference to the Localization of CGRP, VIP and Nitric Oxide (NO).

Lee

Iwanaga

Fujita

1995

Archives of Histology and Cytology

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“…There is a specific and saturable uptake mechanism of PACAP into the brain through the blood-brain barrier, called peptide transport system-6 (22); thus, it is possible that PACAP may also affect brain function through this route. PACAP has been localized to nerve fibers and terminals in the superficial layer of the dorsal horn and cell bodies in the dorsal root ganglia in rats (23). In these nerve fibers, PACAP is partly colocalized with calcitonin gene-related peptide (CGRP) and substance P, suggesting that PACAP is a sensory neurotransmitter.…”

Section: Pacapmentioning

confidence: 99%

The Neuropeptide Pituitary Adenylate Cyclase–Activating Polypeptide and Islet Function

2001

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The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is ubiquitously distributed in both the central and peripheral nervous systems and exerts a variety of effects. PACAP is a neuropeptide in pancreatic islets, where it has been suggested as a parasympathetic and sensory neurotransmitter. PACAP stimulates insulin secretion in a glucose-dependent manner, by an effect executed mainly through augmenting the formation of cAMP and stimulating the uptake of calcium. Accumulating evidence in animal studies points to a physiological importance of PACAP in the regulation of the insulin response to feeding. This review summarizes the current knowledge of islet actions and mechanisms and the function of PACAP. Diabetes 50: 1959

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“…The PAC1 receptor is expressed mainly on neural and smooth muscle cells, while the VPAC1/VPAC2 are localized principally on the dorsal root ganglia (DRG), sensory nerve endings, and inflammatory cells [6,9,50,55,64]. The fact, that PACAP shows increased expression in the superficial layer of the spinal dorsal horn and in capsaicin-sensitive primary sensory neurons, suggested that it has a role in nociception [33,34,39,[61][62][63]. However, the results obtained from the early in vivo studies proved to be contradictory [41].…”

Section: Introductionmentioning

confidence: 99%

Role of Pituitary Adenylate-Cyclase Activating Polypeptide and Tac1 gene derived tachykinins in sensory, motor and vascular functions under normal and neuropathic conditions

et al. 2013

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a b s t r a c tPituitary Adenylate-Cyclase Activating Polypeptide (PACAP) and Tac1 gene-encoded tachykinins (substance P: SP, neurokinin A: NKA) are expressed in capsaicin-sensitive nerves, but their role in nociception, inflammation and vasoregulation is unclear. Therefore, we investigated the function of these neuropeptides and the NK 1 tachykinin receptor (from Tacr1 gene) in the partial sciatic nerve ligationinduced traumatic mononeuropathy model using gene deficient (PACAP −/− , Tac1 −/− , and Tacr1 −/− ) mice. Mechanonociceptive threshold of the paw was measured with dynamic plantar aesthesiometry, motor coordination with Rota-Rod and cutaneous microcirculation with laser Doppler imaging. Neurogenic vasodilation was evoked by mustard oil stimulating sensory nerves. In wildtype mice 30-40% mechanical hyperalgesia developed one week after nerve ligation, which was not altered in Tac1−/− and Tacr1mice, but was absent in PACAP −/− animals. Motor coordination of the PACAP −/− and Tac1 −/− groups was significantly worse both before and after nerve ligation compared to their wildtypes, but it did not change in Tacr1−/− mice. Basal postoperative microcirculation on the plantar skin of PACAP −/− mice did not differ from the wildtypes, but was significantly lower in Tac1 −/− and Tacr1 −/− ones. In contrast, mustard oil-induced neurogenic vasodilation was significantly smaller in PACAP −/− mice, but not in Tacr1 −/− and Tac1 −/− animals. Both PACAP and SP/NKA, but not NK 1 receptors participate in normal motor coordination. Tachykinins maintain basal cutaneous microcirculation. PACAP is a crucial mediator of neuropathic mechanical hyperalgesia and neurogenic vasodilation. Therefore identifying its target and developing selective, potent antagonists, might open promising new perspectives for the treatment of neuropathic pain and vascular complications.

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Pituitary adenylate cyclase activating peptide is a sensory neuropeptide: Immunocytochemical and immunochemical evidence

Cited by 240 publications

References 19 publications

Intraepithelial Nerve Fibers in the Nasal Mucosa of the Rat with Special Reference to the Localization of CGRP, VIP and Nitric Oxide (NO).

Intraepithelial Nerve Fibers in the Nasal Mucosa of the Rat with Special Reference to the Localization of CGRP, VIP and Nitric Oxide (NO).

The Neuropeptide Pituitary Adenylate Cyclase–Activating Polypeptide and Islet Function

Role of Pituitary Adenylate-Cyclase Activating Polypeptide and Tac1 gene derived tachykinins in sensory, motor and vascular functions under normal and neuropathic conditions

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