Physiological effects of platyhelminth FMRFamide-related peptides (FaRPs) on the motility of the monogenean Diclidophora merlangi

The actions of known platyhelminth FaRPs on the contractility of whole-worm preparations of the monogenean, Diclidophora merlangi have been examined in vitro for the first time. All of the peptides tested had excitatory effects on the motor activity of the worm. The order of potency for the peptides tested was: YIRFamide &gt; GYIRFamide = RYIRFamide &gt; GNFFRFamide = FLRFamide. However, although YIRFamide was more potent than GYIRFamide, the latter was the most efficacious on each of the motility parameters (tension, contraction amplitude and contraction frequency) examined at concentrations [ges ]0·1 μm. Serotonin, which stimulates contractility in the worm was used as a positive control. The excitatory activity of turbellarian and cestode neuropeptides on a monogenean indicates at least some structural similarities in the neuropeptide receptors of these classes of flatworm.</jats:p

Comparative in vitro effects of closantel and selected beta-ketoamide anthelmintics on a gastrointestinal nematode and vertebrate liver cells

PNU-87407 and PrNU-88509, beta-ketoamide anthelmintics that are structurally related to each other and to the salicylanilide anthelmintic closantel, exhibit different anthelmintic spectra and apparent toxicity in mammals, The basis for this differential pharmacology was examined in experiments that measured motility and adenosine triphosphate (ATP) levels in larval and adult stages of the gastrointestinal nematode, Haemonchus contortus, and in a vertebrate liver cell line and mitochondria, PNU-87407 and PNU-88509 both exhibited functional cross-resistance with closantel in larval migration assays using closantel-resistant and -sensitive isolates of H, contortus. Each compound reduced motility and,ATP levels in cultured adult H. contortus in a concentration- and time-dependent manner: however, motility was reduced more rapidly by PNU-88509, and ATP levels were reduced by lower concentrations of closantel than the beta-ketoamides. Tension recordings from segments of adult H, contortus showed that PNU-88509 induces spastic paralysis, while PNU-87407 and closantel induce flaccid paralysis of the somatic musculature. Marked differences in the actions of these compounds were also observed in the mammalian preparations. In Chang liver cells, ATP levels were reduced after 3 h exposures to greater than or equal to 0.25 mu M PNU-87407 1 mu M closantel or 10 mu M PNU-88509, Reductions in ATP caused by PNU-88509 were completely reversible, while the effects of closantel and PNU-87407; were irreversible. PNU-87407, closantel and PNU-88509 uncoupled oxidative phosphorylation in isolated rat liver mitochondria, inhibiting the respiratory control index (with glutamate or succinate as substrate) by 50% at concentrations of 0.14, 0.9 and 7.6 mu M respectively

The coordination of heart and gill rhythms in \u3cem\u3eLimulus\u3c/em\u3e

WhenLimulus is exposed to hypoxia both heart rate and ventilation rate decrease together (Fig. 1, Fig. 2A). Hypoxia ultimately leads to cessation of ventilation and concomitant bradycardia. When oxygen is reintroduced into an oxygen free aquarium ventilation resumes rapidly, with a parallel increase in heart rate (Fig. 1, Fig. 2B). Covariation of heart and gill activity similar to that in hypoxia experiments also occurs during the normal respiratory behavior patterns ofLimulus, such as intermittent ventilation, swimming, hyperventilation and gill cleaning. The covariation of heart and ventilation rates is especially evident during transitions of intermittent ventilation (alternating periods of apnea and ventilation, Fig. 3). Covariation is also evident during the large increases in ventilation frequency which occur during hyperventilation and swimming (Fig. 4). Gill cleaning is a centrally determined motor sequence which consists of rhythmic flicking of the inner lobes of a gill plate between the book gill lamellae of the plate on the opposite side. During this behavior there is a marked slowing of the heart rate which is at least as great as the decrease in rate seen during periods of apnea (Figs. 5 and 6). Changes in heart rate associated with ventilatory activity do not appear to be caused by the metabolic demand resulting from such activity (Fig. 7). In addition to frequency covariation of the heart and ventilation rates, there can also be phase coordination of the two rhythms. When the two are close to the same frequency or to harmonic frequencies, the heart often maintains a phase preference with respect to the concurrent gill interval over a considerable period of time (Fig. 8). These results suggest that there are common tonic inputs to both the cardiac ganglion and the central pattern generators for the various ventilatory behaviors, which modulate the frequencies of both simultaneously. Both the frequency covariation and phase communication between the two systems may serve to increase the efficiency of the respiratory-circulatory interactions