Pituitary adenylate cyclase‐activating polypeptide, effects in the human nose

Kinhult, Johan; Adner, Mikael; Uddman, Rolf; Cardell, LO

doi:10.1046/j.1365-2222.2003.01721.x

Cited by 19 publications

(16 citation statements)

References 41 publications

(55 reference statements)

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“…In rodents, PACAP causes relaxation of tracheal smooth muscles (Araki and Takagi, 1992;Conroy et al, 1995;Foda et al, 1995;Hiramatsu et al, 1995;Yoshihara et al, 1997;Berisha et al, 2002;Lindén et al, 2003), promotes bronchodilation (Lindén et al, 1995(Lindén et al, , 1999 and increases nasal airway resistance (Kinhult et al, 2003). The relaxant effect of PACAP on the trachea is mediated through activation of the cAMP/ PKA-dependent (Araki and Takagi, 1992;Kanemura et al, 1993;Foda et al, 1995), NO/cGMP-dependent (Saotome et al, 1998), and carbon monoxide-dependent transduction pathways (Kinhult et al, 2001a).…”

Section: Effects Of Pituitary Adenylate Cyclase-activating Polypepmentioning

confidence: 99%

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

et al. 2009

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Section: Effects Of Pituitary Adenylate Cyclase-activating Polypepmentioning

confidence: 99%

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

et al. 2009

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“…A clinical study involving intranasally administered PACAP demonstrated a potential role for PACAP as a regulator of vascular smooth muscle, secretion, plasma extravasation, neutrophil recruitment, and cytokine activity (73). However, to date, no clinical trials have been performed on investigating the effects of intranasal PACAP on memory or cognition.…”

Section: Pituitary Adenylate Cyclase Activating Polypeptidementioning

confidence: 99%

Intranasal Delivery of Proteins and Peptides in the Treatment of Neurodegenerative Diseases

Meredith

Salameh

Banks

2015

AAPS J

166

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Abstract. The blood-brain barrier (BBB) is a major impediment to the therapeutic delivery of peptides and proteins to the brain. Intranasal delivery often provides a non-invasive means to bypass the BBB. Advantages of using intranasal delivery include minimizing exposure to peripheral organs and tissues, thus reducing systemic side effects. It also allows substances that typically have rapid degradation in the blood time to exert their effect. Intranasal delivery provides the ability to target proteins and peptides to specific regions of the brain when administered with substrates like cyclodextrins. In this review, we examined the use of intranasal delivery of various proteins and peptides that have implications in the treatment of neurodegenerative diseases, focusing especially on albumin, exendin/GLP-1, GALP, insulin, leptin, and PACAP. We have described their rationale for use, distribution in the brain after intranasal injection, how intranasal administration differed from other modes of delivery, and their use in clinical trials, if applicable. Intranasal delivery of drugs, peptides, and other proteins could be very useful in the future for the prevention or treatment of brain related diseases.

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“…PACAP, enhanced the plasma leakage effect of bradykinin, and in 1997 Cardell et al [24] showed that PACAP-38 stimulation of rat skin caused plasma leakage and suggested that it could be due to histamine release. More recent studies showed that in the human nose PACAP-38 increased albumin concentration in nasal secretion fluid, which is a sign of plasma leakage [25]. The selective inhibitor used in our study, a 44-amino acid mutant of the 61-amino acid peptide maxadilan, had minor inflammatory effects (plasma leakage) when applied for 10 min at concentrations 100 times exceeding that of maxadilan.…”

Section: Discussionmentioning

confidence: 57%

“…Studies of the biological effects of PACAP revealed that it enhanced the permeability-inducing effects of bradykinin in the skin of rabbits [22, 23] and rats [24]. Further, in the human nose, PACAP-38 caused extravasation of plasma albumin [25]. It may thus be expected that PACAP and maxadilan could have the same effects in the hamster cheek pouch (HCP), a skin-like tissue without glands and hair follicles.…”

Section: Introductionmentioning

confidence: 99%

Salivary Gland Homogenates of <i>Lutzomyia longipalpis</i> and Its Vasodilatory Peptide Maxadilan Cause Plasma Leakage via PAC1 Receptor Activation

Svensjö

Saraiva²,

Bozza³

et al. 2009

J Vasc Res

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Objectives: Experiments were designed to determine if salivary gland homogenates (SGH) of the sand fly Lutzomyia longipalpis, the vasodilatory peptides maxadilan and pituitary adenylate cyclase-activating peptide (PACAP-38) may cause plasma leakage and to what extent these effects could be due to PAC1 receptor stimulation. Methods: Using FITC-dextran as a plasma marker, intravital microscopy of the hamster cheek pouch (HCP) and a digital camera were used to assess arteriolar diameter and fluorescence of a selected area (5 mm²) representative of the HCP microcirculation. Results: Cheek pouches prepared for intravital microscopy and exposed to topical application of SGH, maxadilan or PACAP-38 developed maximal dilation of arterioles in the range of 20–60 μm within 10 min, and this effect lasted for 30–90 min. The increase in fluorescence intensity induced by each of these compounds was due to plasma leakage from postcapillary venules. The mutant peptide of maxadilan (M-65), a PAC1 receptor antagonist, inhibited both dilation and plasma leakage induced by SGH or maxadilan. Plasma leakage induced by SGH was modestly inhibited by the bradykinin B₂ receptor antagonist HOE-140, but not by the antihistamine mepyramine or the nitric oxide synthase inhibitor L-NA. Conclusions: SGH of L. longipalpis and its vasodilatory peptide maxadilan caused long-lasting arteriolar dilation and plasma leakage in the cheek pouch via PAC1 receptor activation.

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Pituitary adenylate cyclase‐activating polypeptide, effects in the human nose

Abstract: These results imply that PACAP is an important endogenous mediator in human upper airways, with a potential role as a regulator of vascular smooth muscle, secretion, plasma extravasation, neutrophil recruitment and cytokine activity.

Cited by 19 publications

References 41 publications

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

Intranasal Delivery of Proteins and Peptides in the Treatment of Neurodegenerative Diseases

Salivary Gland Homogenates of <i>Lutzomyia longipalpis</i> and Its Vasodilatory Peptide Maxadilan Cause Plasma Leakage via PAC1 Receptor Activation

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