Cytotoxic effect and electrophysiologic activity of (R)-bgugaine, an alkylpyrrolidine alkaloid against MRC-5 fibroblasts.

The cytotoxicity and the electrophysiological effects against MRC-5 fibroblasts of 2-alkylpyrrolidine, (-)-R-bgugaine [1], a natural alkaloid, extracted from Arisarum vulgare Targ., (Araceae) were studied. This compound showed a cytotoxic potential against MRC-5 fibroblasts at 10 microg/ml. The electrophysiological study of this molecule on MRC-5 cells was carried out using the technique of patch-clamp and showed that (-)-R-bgugaine [1] has a sub-maximum effect on the outward potassium (current) at the concentration of 1 microM (0.281 microg/ml). In this study we show that R-bgugaine [1] activates the outwards potassium (current) activated by intracellular calcium.

Effects of lingual nerve afferents on swallowing in sheep.

We investigated in sheep the effects of stimulation of the thick afferent fibers running through the lingual nerve (LN) upon the activity of some of the muscles and medullary interneurons or motoneurons which are active during swallowing. Using electromyography (EMG), and extra- and intracellular neuronal recording, we demonstrated that LN stimulation inhibited triggering and/or distal progression of deglutition reflexly induced by stimulation of the superior laryngeal nerve (SLN). This inhibition appeared as a delay, or the interruption or total suppression, of the EMG and neuronal swallowing activities, depending on the interval between SLN and LN stimulation. It was apparent at the level of the muscles and motoneurons of the nucleus ambiguus, as well as at the level of the interneurons of the dorsal medulla within or around the nucleus of solitary tract, which are assumed to be the core of the organizing system for swallowing, the so-called central pattern generator (CPG). Taking into account the stimulation parameters used in our experiments, it was likely that only LN-mechanosensitive fibers were excited. These fibers were involved in the jaw-opening reflex, and possibly in mastication regulation. Therefore, inhibition of swallowing could result from interactions between the hindbrain mastication and swallowing CPGs. However, it was also possible that mechanosensitive afferents acted upon the swallowing CPG directly or indirectly through supramedullary, especially cortical, loops.

Cytotoxic effect and electrophysiological activity of (S)-bgugaine, an alkylpyrrolidine alkaloid against MRC-5 fibroblasts.

(+)-S-bgugaine [1], is an alkaloid prepared by enantioselective synthesis. This alkaloid is an isomer of R-bgugaine [2], an alkaloid isolated from Arisarum vulgare, an Araceae toxic plant of Morocco. The cytotoxic effect and the electrophysiological activity of (+)-S-bgugaine [1] against MRC-5 fibroblasts of (+)-S-bgugaine 1, were studied. (+)-S-bgugaine [1] showed a cytotoxic potential at 40 microg/ml against these MRC-5 cells. The electrophysiological study on MRC-5 cells was carried out using the technique of patch-clamp and showed that the activity of compound 1 involved a reduction of outward potassic current at the concentration of 100 microM (28.1 microg/ml) and was accentuated by 200 microM (56.2 microg/ml). In this study we show that S-bgugaine [1], decreases the outward potassic current.

Stimulation of the chewing area of the cerebral cortex induces inhibitory effects upon swallowing in sheep.

Mastication and swallowing are two tightly integrated components of food intake behavior. We investigated the effects of stimulating the chewing area of the fronto-orbital cortex (CCx) on some muscles and medullary interneurons (Ins) or motoneurons (Mns) active during swallowing. For the purpose of comparison, the lingual nerve (LN) was also stimulated during the experiments. Electromyography (EMG) and extracellular neuronal recording were used, and swallowing was reflexly induced (RIS) by stimulation of the superior laryngeal nerve (SLN). RIS was almost totally abolished during long-lasting repetitive stimulation of CCx or LN, and was strongly facilitated after stimulation cessation. Short-duration stimulation (one or a few pulses) of both the CCx and LN also inhibited triggering of deglutition when delivered just before the onset of RIS. This inhibition appeared as a delay or total suppression of the EMG and neuronal swallowing activities. It was obvious at the level of the muscles, the hypoglossal Mns and the premotoneurons (PMns; Ins of the ventral medulla near the nucleus ambiguus), as well as at the level of the Ins of the dorsal medulla (within or around the solitary tract nucleus) which are assumed to be the core of the 'central pattern generator' (CPG) for swallowing. In addition to the 'chewing-related inhibition', many ventral Ins exhibited a short latency synaptic activation after CCx and/or LN stimulation. Therefore, these Ins may play a pivotal role for reflex or cortical fast control of tongue (and jaw) muscles, and for coordinating their contractions in the context of mastication-deglutition interactions.

Effects of lingual nerve and chewing cortex stimulation upon activity of the swallowing neurons located in the region of the hypoglossal motor nucleus.

This study focuses on motoneurons and interneurons in the region of the hypoglossal nucleus (XIIth) related to swallowing and chewing. In sheep anesthetized with halothane, we have used extracellular microelectrodes to study the effects of stimulation of the superior laryngeal nerve (SLN), the lingual nerve (LN) and the chewing cortex (CCx) upon activities of the swallowing neurons (SNs). Ipsilateral stimulation (1-5 pulses at 500 Hz) of the peripheral afferents or CCx did not generally induce a short latency activation of the hypoglossal swallowing motoneurons (Group I SNs) since only 4 motoneurons (69 tested) were activated by the SLN, 4 motoneurons (56 tested) by the LN and none by the CCx. In contrast, the same stimulations were more effective with swallowing interneurons (Group II SNs) located in the reticular formation close to the XIIth motor nucleus since 12 neurons (30 tested) were activated with short latencies (9 +/- 1.8 ms; mean latency +/- S.D.) by the SLN, 9 neurons (21 tested) by the LN (latency; 8 +/- 1.8 ms) and 5 neurons (18 tested) by the CCx (latency: 13 +/- 1.7 ms). Seven neurons were activated by two or three modes of stimulation indicating the existence of convergent inputs upon some Group II SNs. During chewing movements induced by a prolonged stimulation (20-40 Hz) of the CCx, 10 Group I SNs (16 tested) versus only one Group II SN (8 tested) were found to fire in association with the jaw opening. Moreover, 3 motoneurons and 4 interneurons inactive during swallowing discharged during chewing movements.(ABSTRACT TRUNCATED AT 250 WORDS)

Activity of extrinsic tongue muscles during swallowing in sheep.

The participation of extrinsic muscles of the tongue in swallowing reflexly induced by stimulation of the superior laryngeal nerve was studied in 7 anesthetized sheep. The tongue retractor muscles (styloglossus and hyoglossus) always discharged in synergy with the suprahyoid (geniohyoid) and jaw (anterior digastric and medial pterygoid) muscles. The main protrusor muscle of the tongue, the genioglossus, was inactive in 5 animals and active in 2. The significance of this muscular synergy is discussed.