Different Ion Channel Control pH6‐Induced Bronchoconstriction and Calcitonin Gene‐Related Peptide Release in the Guinea‐Pig Lung

Abstract

Abstrrrcr:We have studied the bronchoconstriction and the release of calcitonin gene-related peptide-like immunoreactivity induced by perfusion of pH6 buffer in the isolated guinea-pig perfused lung. Both bronchoconstriction and peptide release were completely abolished after systemic capsaicin pretreatment. Ca2+-free pH6 buffer infusion also completely inhibited the bronchial response, whereas the calcitonin gene-related peptide-like immunoreactivity overflow was significantly reduced. w-Conotoxine and w-agatoxin IVA known as N-, L-and P-type Ca2+ channel blocker, respectively, and the Na+ channel blocker tetrodotoxin decreased significantly the pH6-induced bronchial response and calcitonin gene-related peptide like immunoreactivity overflow. Nifedipine was without influence suggesting the involvement of both P-and N-type Ca2+ channel as well as the activation of an axon reflex. Ruthenium red had a more pronounced reduction effect on the functional response than on the peptide release. Ryanodine and caffeine are both agents known to influence Ca2+ release from sarcoplasmic reticulum. Ryanodine significantly reduced both bronchoconstriction and calcitonin gene-related peptide-like immunoreactivity overflow. Caffeine as well as theophylline and the Na+-H+ blocker, dimethylamiloride, largely depressed the functional response while producing a significant increase of calcitonin gene-related peptide-like immunoreactivity basal value. The pH6-induced peptide overflow was slightly inhibited after caffeine and dimethylamiloride pretreatment whereas no significant change was observed after theophylline. It is concluded that multiple ion channels including different type of Ca2+ channels appear to participate in pH6-induced bronchoconstriction and calcitonin gene-related peptide-like immunoreactivity release in the guinea-pig lung.

Effects of coffee and caffeine on bladder dysfunction in streptozotocin-induced diabetic rats1

“…In addition, previous studies showed that caffeine may have protective and nutritive effects on neurons to prevent and treat Parkinson's disease and migraine; stimulate release of calcitonin gene-related peptide [26] , which is recognized as one of the most important sensory neurotrans-ducers and neuromodulators in the bladder to improve the impaired sensation of bladder fullness in diabetic rats [27] ; and influence neuromuscular functions as the antagonist of adenosine receptors in vivo.…”

“…As was stated above, we suggest that the mechanism for the effect on the bladder is as follows: (i) by increasing cAMP content in the bladder recovery of the micturition reflex and improvement of the detrusor contractility was shown; (ii) during the storage phase, caffeine may reduce spontaneous contraction overactivity in a detrusor instability model [21] , and thus benefits bladder compliance; (iii) histopathological studies showed that caffeine could protect the ultrastructures of intracellular sarcoplasmic reticulum, mitochondria, and so on, in the bladder muscle of diabetic rats (unpublished our data). In addition, previous studies showed that caffeine may have protective and nutritive effects on neurons to prevent and treat Parkinson's disease and migraine; stimulate release of calcitonin gene-related peptide [26] , which is recognized as one of the most important sensory neurotrans-ducers and neuromodulators in the bladder to improve the impaired sensation of bladder fullness in diabetic rats [27] ; and influence neuromuscular functions as the antagonist of adenosine receptors in vivo.…”