Methyl palmitate modulates the nicotine-induced increase in basilar arterial blood flow.

Methyl palmitate (MP) is a fatty acid methyl ester. Our recent study indicated that adrenergic nerve-dependent functional sympathetic-sensory nerve interactions were abolished by MP in mesenteric arteries. However, the effect of MP on perivascular nerves and cerebral blood flow remains unclear. In this study, the increase in basilar arterial blood flow (BABF) after the topical application of nicotinic acetylcholine receptor agonists was measured using laser Doppler flowmetry in anesthetized rats. The choline (a selective α7-nicotinic acetylcholine receptor agonist)-induced increase in BABF was abolished by tetrodotoxin (a neurotoxin), NG -nitro-L-arginine (a nonselective NO synthase inhibitor), α-bungarotoxin (a selective α7-nicotinic acetylcholine receptor inhibitor), and chronic sympathetic denervation. In addition, the nicotine (a nicotinic acetylcholine receptor agonist)-induced increase in BABF was inhibited by MP in a concentration-dependent manner. The acetylcholine-induced increase in BABF was not affected by MP. The myography results revealed that nicotine-induced vasorelaxation was significantly inhibited by MP, but was reversed by chelerythrine (a protein kinase C inhibitor). MP-induced vasodilation was significantly greater in BA rings without endothelium compared to those with endothelium. Meanwhile, MP did not affect baseline BABF. Our results indicate that MP acts as a neuromodulator in the cerebral circulation where it activates the PKC pathway and causes a diminished nicotine-induced increase in blood flow in the brainstem, and that the vasorelaxation effect of MP may play a minor role.

Capsaicin-Sensitive Sensory Nerves Indirectly Modulate Motor Function of the Urinary Bladder / 대한배뇨장애요실금학회지

PURPOSE: The urinary bladder (UB) is innervated by both sensory and autonomic nerves. Recent studies have shown that sensory neuropeptides induced contractions in the detrusor muscle. Therefore, in a mouse model, we investigated the presence of interactions between the submucosal sensory nerves and the autonomic nerves that regulate the motor function of the detrusor muscle. METHODS: UB samples from male C57BL/6 mice were isolated, cut into strips, and mounted in an organ bath. Dose-response curves to norepinephrine and phenylephrine were studied in UB strips with and without mucosa, and the effects of preincubation with a receptor antagonist and various drugs on relaxation were also studied using tissue bath myography. RESULTS: Phenylephrine-induced relaxation of the UB strips showed concentration-related effects. This relaxation appeared in both mucosa-intact and mucosa-denuded UB strips, and was significantly inhibited by lidocaine, silodosin, and guanethidine (an adrenergic neuronal blocker). Meanwhile, phenylephrine-induced relaxation was inhibited by pretreatment with propranolol and calcitonin gene-related peptide (CGRP)–depletory capsaicin in UB strips with and without mucosa. CONCLUSIONS: The present study suggests that phenylephrine activates the α-1A adrenergic receptor (AR) of the sensory nerve, and then activates capsaicin-sensitive sensory nerves to release an unknown substance that facilitates the release of norepinephrine from adrenergic nerves. Subsequently, norepinephrine stimulates β-ARs in the detrusor muscle in mice, leading to neurogenic relaxation of the UB. Further animal and human studies are required to prove this concept and to validate its clinical usefulness.