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Modulation of serotonin-controlled behaviors by Go in Caenorhabditis elegans.

Seven transmembrane receptors and their associated heterotrimeric guanine nucleotide-binding proteins (G proteins) have been proposed to play a key role in modulating the activities of neurons and muscles. The physiological function of the Caenorhabditis elegans G protein Go has been genetically characterized. Mutations in the goa-1 gene, which encodes an alpha subunit of Go (G alpha o), cause behavioral defects similar to those observed in mutants that lack the neurotransmitter serotonin (5-HT), and goa-1 mutants are partially resistant to exogenous 5-HT. Mutant animals that lack G alpha o and transgenic animals that overexpress G alpha o [goa-1(xs) animals] have reciprocal defects in locomotion, feeding, and egg laying behaviors. In normal animals, all of these behaviors are regulated by 5-HT. These results demonstrate that the level of Go activity is a critical determinant of several C. elegans behaviors and suggest that Go mediates many of the behavioral effects of 5-HT.

Animals↗

Clinical and urodynamic effects of norfenefrine in women with stress incontinence.

20 women with stress incontinence were treated with an alpha-adrenoceptor stimulating agent norfenefrine (Nevadral Retard) for 3 months. The mean dose administered was 60 mg given in slow-release tablets. Significant beneficial effect on the symptom and the 'sign' of stress incontinence was found as well as a significant increase in the maximum urethral closure pressure. 7 patients (35%) became subjectively and objectively continent. Only minor side effects were observed during treatment.

2-Hydroxyphenethylamine↗

Norfenefrine in the treatment of female stress incontinence. A double-blind controlled trial.

Forty-four consecutive patients with genuine stress incontinence were treated with norfenefrine 15-30 mg t.i.d. in a 6-week, double-blind and parallel, placebo-controlled study. Subjectively, 52% were improved and 26% became continent during norfenefrine treatment. Objectively (stress test), 30% became continent and the maximum urethral closure pressure increased 10% which was statistically significant. These results, however, were not statistically different from those of placebo treatment. Simultaneously, subjective and objective improvement was seen more often in patients given norfenefrine compared to placebo (p less than 0.1). In patients with most severe incontinence according to urodynamic criteria the effect of norfenefrine was statistically significantly better than placebo. A low incidence of side effects was observed and no differences between norfenefrine and placebo were found. It is concluded that norfenefrine may be of value in the treatment of female stress incontinence.

2-Hydroxyphenethylamine↗

Does medical therapy cure female stress incontinence?

Forty-four consecutive female patients, who were scheduled for operation for genuine stress incontinence but instead treated pharmacologically with an alpha-agonist or placebo for 3-4.5 months, were evaluated after a median observation period of 30 months. Ten patients (23%) underwent colposuspension. Fourteen patients (32%) claimed to be continent or so much improved that further treatment was considered unnecessary by the patients themselves. Of the remaining 20 patients who still claimed to have stress incontinence, 11 (25%) preferred to resume the pharmacological treatment whereas 9 patients (20%) had not decided whether they wanted further treatment. These results suggest that some operations for stress incontinence may be avoided by introduction of a standard trial of medical therapy prior to intended surgical intervention.

2-Hydroxyphenethylamine↗

Norfenefrine in the treatment of female urinary stress incontinence assessed by one-hour pad weighing test.

Thirty-three women with urinary stress incontinence were treated with the alpha-adrenoceptor-stimulating agent, norfenefrine (Nevadral Retard). Treatment was administered during 3-24 weeks at a daily dosage of 90 mg. Judged by a 1-hour pad weighing test, a significant effect could be demonstrated. With the exception of 1 case of allergic reaction and 1 case of recurrent vomiting, a simultaneously performed tolerability test revealed only minor side effects.

2-Hydroxyphenethylamine↗

Acute effect of norfenefrine on the urethral pressure profile in females with genuine stress incontinence.

To study the acute effect of norfenefrine, given orally in aqueous solution, on the urethral closure function, profilometry was performed before and after administration of placebo and increasing doses of norfenefrine in 6 females with genuine stress incontinence. A weak increase in urethral pressure was observed after administration of 90 mg of norfenefrine. No changes in heart rate and blood pressure occurred. The results indicate that the direct sympathomimetic effect of norfenefrine is weak. It is suggested that norfenefrine mainly acts via indirect mechanisms.

Female↗

Effects of D2343, a new beta-mimetic drug, and terbutaline on spontaneous term labor.

The effects of an intravenous bolus injection of D2343 (0.75 or 1 mg) or terbutaline (0.25 mg) on spontaneous term labor were studied. The uterine activity was recorded by a transducer-tipped intrauterine catheter and calculated electronically by an uterine activity integrator module built in a conventional fetal monitor. After drug administration the uterine activity was reduced to a similar extent with D2343 and terbutaline but the contractions were abolished for a longer time with terbutaline injection (mean of 9.3-9.8 min compared with 17.0 min). Maternal blood pressure was unaffected in both groups but the increase in pulse rate was slightly higher in the D2343 groups. D2343 seems to have an effect ratio between uterine inhibitory capacity and cardiovascular side effects similar to terbutaline.

Adult↗

Neuromodulation in invertebrate sensory systems: from biophysics to behavior.

Neuromodulation may enhance the ability of sensory circuits to respond appropriately to widely variable environmental stimuli. The functional significance of neuromodulation will emerge from understanding the effects of modulators not just on single cells and synapses, but also on networks and the behavior of intact animals. With their relatively simple circuitry and large identifiable cells, invertebrate nervous systems offer insights into the complex roles of neuromodulators in modifying networks to meet the changing needs of the animal. Here we describe the role of neuromodulation in several invertebrate sensory systems that have been studied at a variety of levels, from the biophysical up to the behavioral.

Animals↗

Insect cardioactive peptides. I. Distribution and molecular characteristics of two cardioacceleratory peptides in the tobacco hawkmoth, Manduca sexta.

Using an in vitro heart bioassay, the pharmacological and biochemical properties of two cardioactive peptides derived from neural tissues of the moth, Manduca sexta, were analysed. Gel filtration of ventral nerve cords (VNC) from pharate adults identified two cardioacceleratory peptides (CAP1 and CAP2) with apparent molecular weights of 1000 and 500 Da, respectively. Both CAPs were localized to the abdominal perivisceral organs, the major neurohaemal release sites in the insect VNC. Pulse application of CAP1 or CAP2 on the in vitro Manduca heart produced a dose-dependent increase in rate but had no effect on beat amplitude. The threshold dose for the action of each peptide on the isolated heart bioassay was less than 0.05 abdominal nerve cord equivalents. Both CAPs were present in the pharate adult VNC of several other Lepidopteran species. Neither CAP1 nor CAP2 was detected in the prepupal VNC of Manduca sexta.

Animals↗