M6 Membrane Protein Plays an Essential Role in Drosophila Oogenesis

We had previously shown that the transmembrane glycoprotein M6a, a member of the proteolipid protein (PLP) family, regulates neurite/filopodium outgrowth, hence, M6a might be involved in neuronal remodeling and differentiation. In this work we focused on M6, the only PLP family member present in Drosophila, and ortholog to M6a. Unexpectedly, we found that decreased expression of M6 leads to female sterility. M6 is expressed in the membrane of the follicular epithelium in ovarioles throughout oogenesis. Phenotypes triggered by M6 downregulation in hypomorphic mutants included egg collapse and egg permeability, thus suggesting M6 involvement in eggshell biosynthesis. In addition, RNAi-mediated M6 knockdown targeted specifically to follicle cells induced an arrest of egg chamber development, revealing that M6 is essential in oogenesis. Interestingly, M6-associated phenotypes evidenced abnormal changes of the follicle cell shape and disrupted follicular epithelium in mid- and late-stage egg chambers. Therefore, we propose that M6 plays a role in follicular epithelium maintenance involving membrane cell remodeling during oogenesis in Drosophila

Bradykinin receptor blockade reduces sympathetic nerve response to muscle contraction in rats with ischemic heart failure

Previous animal and human studies have suggested that a muscle reflex engaged during contraction leads to heightened levels of sympathetic activity in congestive heart failure (CHF). The present experiment was designed to test the role for bradykinin, which is produced within contracting skeletal muscle and contributes to the muscle reflex through its action on kinin B2 receptors located on the endings of thin fiber muscle afferents. CHF was induced in rats by myocardial infarction (MI) after coronary artery ligation. Echocardiography was performed to determine fractional shortening (FS), an index of the left ventricular function. In the decerebrate rats, we examined renal sympathetic nerve activity (RSNA) during 1 min intermittent (1 to 4 s stimulation to relaxation) contraction of left triceps surae muscles. RSNA responded synchronously as tension was developed, and the response was significantly (P < 0.05) greater in MI rats [+39 ± 9% s−1 (integrated RSNA over time); n = 16] with 20 ± 2% of FS than that in control healthy rats (+19 ± 2% s−1; n = 16) with 49 ± 2% of FS. Tension development did not differ significantly between the two groups of rats. Thirty minutes after intra-arterial injection into the hindlimb circulation of the kinin B2 receptor antagonist, HOE-140 (2 μg/kg), the RSNA response to contraction was significantly reduced in the MI rats (+26 ± 7% s−1) but not in the control rats (+17 ± 2% s−1). These data suggest that bradykinin within contracting muscle is part of the exaggerated muscle reflex seen in CHF

Local adenosine receptor blockade accentuates the sympathetic responses to fatiguing exercise

The role adenosine plays in evoking the exercise pressor reflex in humans remains controversial. We hypothesized that localized forearm adenosine receptor blockade would attenuate muscle sympathetic nerve activity (MSNA) responses to fatiguing handgrip exercise in humans. Blood pressure (Finometer), heart rate, and MSNA from the peroneal nerve were assessed in 11 healthy young volunteers during fatiguing isometric handgrip, postexercise circulatory occlusion (PECO), and passive muscle stretch during PECO. The protocol was performed before and after adenosine receptor blockade by local infusion of 40 mg aminophylline in saline via forearm Bier block (regional intravenous anesthesia). In the second experiment, the same amount of saline was infused via the Bier block. After aminophylline, the MSNA and blood pressure responses to fatiguing handgrip, PECO, and passive stretch (all P < 0.05) were significantly greater than during the control condition. Saline Bier block had no similar effects on the MSNA and blood pressure responses. These data suggest that adenosine receptor antagonism in the exercising muscles may accentuate sympathetic activation during fatiguing exercise