Attenuation of relaxing response induced by pituitary adenylate cyclase-activating polypeptide in bronchial smooth muscle of experimental asthma

Abstract

Bronchomotor tone is regulated by contraction and relaxation of airway smooth muscle (ASM). A weakened ASM relaxation might be a cause of the airway hyperresponsiveness, a characteristic feature of bronchial asthma. Pituitary adenylyl cyclase-activating polypeptide (PACAP) is known as a mediator that causes ASM relaxation. To date, whether or not the PACAP responsiveness is changed in asthmatic ASM is unknown. The current study examined the hypothesis that relaxation induced by PACAP is reduced in bronchial smooth muscle (BSM) of allergic asthma. The ovalbumin (OA)-sensitized mice were repeatedly challenged with aerosolized OA to induce asthmatic reaction. Twenty-four hours after the last antigen challenge, the main bronchial smooth muscle (BSM) tissues were isolated. Tension study showed a BSM hyperresponsiveness to acetylcholine in the OA-challenged mice. Both quantitative RT-PCR and immunoblot analyses revealed a significant decrease in PAC1 receptor expression in BSMs of the diseased mice. Accordingly, in the antigen-challenged group, the PACAP-induced PAC1 receptor-mediated BSM relaxation was significantly attenuated, whereas the relaxation induced by vasoactive intestinal polypeptide was not changed. These findings suggest that the relaxation induced by PACAP is impaired in BSMs of experimental asthma due to a down-regulation of its binding partner PAC1receptor. Impaired BSM responsiveness to PACAP might contribute to the AHR in asthma.

The role of human mast cells in allergy and asthma

“…Mast cells express MRGPRX2 which acts as PACAP receptor and can trigger degranulation of mast cells [ 74 ]. PACAP also induces bronchial muscle relaxation, which has been demonstrated in human cells in vitro and in mice with asthma in vivo [ 75 , 76 ].…”

Female reproductive functions of the neuropeptide PACAP

“…In the periphery ( 19 , 20 ), several actions have been described regarding the cardiovascular system, where the peptide influences cardiac neuronal excitability and heart muscle contractility ( 21 ). In the gastrointestinal and respiratory tract PACAP plays a role in neuroendocrine secretion, smooth muscle contractility and blood supply ( 22 , 23 ). Endocrine glands show high levels of expression of PACAP and the peptide is involved in secretion of several hormones ( 19 – 23 ).…”

Protective Effects of PACAP in a Rat Model of Diabetic Neuropathy

“…PACAP has a widespread distribution in the body, with the highest expression levels in the nervous system and endocrine glands, where it acts as a neurotransmitter, neuromodulator, and neurohormone [ 2 , 3 , 4 , 5 , 6 ]. In addition, PACAP and its receptors are widely expressed in peripheral organs [ 1 , 7 , 8 , 9 , 10 ], and the peptide plays different roles in numerous physiological processes in the cardiovascular, respiratory, urogenital, musculoskeletal, and digestive systems [ 11 , 12 , 13 , 14 , 15 , 16 ]. One of the established effects of the neuropeptide is its neurotrophic/neuroprotective action [ 17 , 18 , 19 , 20 , 21 , 22 ].…”

“…Sci. 2021, 22, 10691 2 of 18 organs [1,[7][8][9][10], and the peptide plays different roles in numerous physiological processes in the cardiovascular, respiratory, urogenital, musculoskeletal, and digestive systems [11][12][13][14][15][16]. One of the established effects of the neuropeptide is its neurotrophic/neuroprotective action [17][18][19][20][21][22].…”