Prostaglandin analogues and uterotonic potency: A comparative study of seven compounds

The uterotonic potency of seven prostaglandin analogues has been investigated using the single intravenous injection technique and comparison of threshold uterine contractility achieved during continuous intravenous infusion. The degree and duration of uterine stimulation in response to graded doses of some of the analogues was also evaluated following intra-amniotic, oral and vaginal administration. 17-Phenyl substituted PGE₂ and PGF_2α are reported upon for the first time. Among the prostaglandin compounds tested, the free acid of 16,16-dimethyl PGE₂ not only is the most potent compound but it may also have great potential for clinical application as an easily administered vaginal abortifacient.     

Anhydrolevuglandin D2 inhibits the uterotonic activity of prostaglandins F2 alpha and D2

Anhydrolevuglandin D2 (AnLGD2), which is produced from PGH2 by a water-induced rearrangement and subsequent dehydration, is uterotonic. However, increasing concentrations caused decreased responses of the uterine horns. AnLGD2 inhibited responses of uteri to stimulation by specific prostaglandins. PGF2 alpha was inhibited at an AnLGD2:PGF2 alpha ratio of 0.05:1 with 5 to 25 pg/ml concentrations of PGF2 alpha. The response to PGD2 was inhibited at an AnLGD2:PGD2 ratio of 0.05:1 with PGD2 concentrations of 5 to 75 pg/ml. In contrast, the uterotonic effects of PGE2 were not inhibited by AnLGD2. When AnLGD2 was added to baths with contracting uteri it inhibited contractions less if the exposure period was 5 min than if it was 10 min. The longer exposure times produced prolonged inhibition of contractile activity with bath concentrations of AnLGD2 as little as 2.5 pg/ml.     

Acyclic precursors of the uterotonic oxepane diterpenoids of ‘zoapatle’ (Montanoa tomentosa)

Chemical analysis of Montanoa tomentosa yielded, in addition to the known biologically active oxepane diterpenoids zoapatanol, tomentol and tomexanthol, three new uterotonic acyclic diterpenoids, which are considered the precursors of the oxepane derivatives mentioned above. The structures of the new compounds were established by spectroscopic methods.     

Oxytocin enhances the basal release of uterine prostaglandin F2 alpha, but not that of PGE1, or of PGE2, and changes the metabolism of exogenous arachidonate, favouring the formation of prostaglandin F2 alpha and 5-HETE. Relationships with its uterotonic action and modulation by estradiol

We attempted to explore possible mechanism(s) subserving the influence of oxytocin on uterine motility by studying the action of the hormone on: 1) the contractile activity of isolated rat uteri in the presence or absence of indomethacin; 2) the synthesis and release of prostaglandins (PGs) into the solution incubating the uterine tissue as well as the metabolism of labelled arachidonic acid; 3) the uptake of 45Ca2+ by uterine strips. The experiments were bone with uterine preparations isolated from spayed rats treated or not with 17-beta-estradiol. The values of isometric developed tension (IDT) and of frequency of contractions (FC) induced by oxytocin in uterine strips isolated from spayed and spayed-estrogenized rats, were not modified by indomethacin at 10(-6) M. On the other hand, uterine strips from untreated spayed rats, release into the incubating medium approximately equal amounts of PGE1, PGE2 and PGF2 alpha. The in vitro presence of oxytocin (50 mU/ml) increased significantly (p 0.05) the output of PGF 2 alpha without changing the release of PGE1 or PGE2. Uteri from spayed rats injected prior to sacrifice with 17-beta-estradiol released significantly less PGE1 and PGE2 (p less than 0.005) than preparations from non-injected animals, whereas the output of PGF2 alpha in the suspending solution remained unchanged. Following estrogenization the addition of oxytocin to preparations obtained from spayed-estrogenized rats also increased the output of uterine PGF2 alpha (p less than 0.001) without changing that of PGs E1 or E2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Investigation of the mechanism of temperature sensitivity of the electroreceptors of ampullae of lorenzini

In experiments on Black Sea skates (Raja clavata), the potential of the receptor epithelium of the ampullae of Lorenzini and spike activity of single nerve fibers connected to them were investigated during electrical and temperature stimulation. Usually the potential within the canal was between 0 and –2 mV, and the input resistance of the ampulla 250–400 k. Heating of the region of the receptor epithelium was accompanied by a negative wave of potential, an increase in input resistance, and inhibition of spike activity. With worsening of the animal's condition the transepithelial potential became positive (up to +10 mV) but the input resistance of the ampulla during stimulation with a positive current was nonlinear in some cases: a regenerative spike of positive polarity appeared in the channel. During heating, the spike response was sometimes reversed in sign. It is suggested that fluctuations of the transepithelial potential and spike responses to temperature stimulation reflect changes in the potential difference on the basal membrane of the receptor cells, which is described by a relationship of the Nernst's or Goldman's equation type.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. I. M. Sechenov, Institute of Evolutionary Physiology and Biochemistry, Academy of Sciences of the USSR, Leningrad. Pacific Institute of Oceanology, Far Eastern Scientific Center, Academy of Sciences of the USSR, Vladivostok. Translated from Neirofiziologiya, Vol. 12, No. 1, pp. 67–74, January–February, 1980.     

Principles of organization and evolution of systems of regulation of functions

Evolution of living organisms is closely connected with evolution of structure of the system of regulations and its mechanisms. The functional ground of regulations is chemical signalization. As early as in unicellular organisms there is a set of signal mechanisms providing their life activity and orientation in space and time. Subsequent evolution of ways of chemical signalization followed the way of development of delivery pathways of chemical signal and development of mechanisms of its regulation. The mechanism of chemical regulation of the signal interaction is discussed by the example of the specialized system of transduction of signal from neuron to neuron, of effect of hormone on the epithelial cell and modulation of this effect. These mechanisms are considered as the most important ways of the fine and precise adaptation of chemical signalization underlying functioning of physiological systems and organs of the living organism