Comparative biochemistry and physiology. C: Comparative pharmacology最新文献

1. The blocking action of δ-philanthotoxin (PhTX-4.3.3), a polyamine amide wasp toxin, and 33 structural analogues was studied at the nicotinic acetylcholine receptor of isolated neuronal somata from locust thoracic ganglia and at the cockroach cercal nerve-giant interneuron nicotinic cholinergic synapse.

2. A comparison of the structure-activity relationships reported here for the locust somal and cockroach synaptic nicotinic receptors and for the glutamatergic neuromuscular synapses of housefly larvae reported previously suggests a generally similar pharmacology for the channel-blocking action at ligand-activated ion channels, but with differences that might be due to variation in accessibility between synaptic receptors and those on the neuronal somata or to genuine divergence in ligand-activated ion channel pharmacology.

1. Novel antitumor and antimicrobial glycoproteins were found in the sea hares. These glycoproteins were purified to apparent homogeneity from Aplysia kurodai, Aplysia Juliana and Dolabella auricularia, and designated as aplysianins, julianins and dolabellanins, respectively.

2. The nine isolated glycoproteins lysed all the tumor cells tested but did not lyse normal white and red blood cells.

3. The glycoproteins completely inhibited the synthesis of DNA and RNA by tumor cells within 2 hr and caused tumor lysis within 15hr.

4. Tumor lysis was inhibited by the presence of N-acetylneuraminic acid, suggesting that the recognition of the sugar moiety is a key step in the cytolysis by antitumor glycoproteins from sea hares.

5. These antitumor glycoproteins, except dolabellanin P, also showed antimicrobial activities.

6. The factors were active for Gram-positive and -negative bacteria and some fungi, and their action was not cytocidal but cytostatic.

7. They exerted the antibacterial action by inhibiting nucleic acid synthesis, as does a DNA-inhibiting chemotherapeutic drug.

8. The sequence of the N-terminal part of dolabellanin A was similar to other antibacterial peptides from arthropoda, amphibia and mammals, suggesting that dolabellanin-like antibacterial peptides are common throughout the animal kingdom.

1. Immunocytochemical investigations in normal and regenerated eyes of Helix aspersa Müller revealed a positive immunoreactivity toward antibodies directed against four biologically active peptides.

2. Eighty per cent of tentaculectomized animals regenerated all tentacular structures and the immunoreactivity was found to be identical in normal and regenerated retinas.

3. Type I photosensory cells are the only αMSH-positive structures, whereas the reactivity to the three other antibodies is localized in one (rarely two) retinal ganglion cell(s).

4. Using an elution technique, the colocalization of the three substances has been demonstrated in a unique ganglion cell.

5. These results seem to indicate that the α MSH-like substance(s) play(s) an important role in visual mechanisms, particularly in photoreception.

6. The colocalization of the three other substances in a unique ganglion cell suggests their probable crucial neuromodulatory and/or neurotransmitter function in rapid conduction of impulses to the brain.

1. [³H]Batrachotoxinin A-20-α-benzoate ([³H]BTX-b) and [³H]saxitoxin ([³H]STX), radioligands that bind to distinct sites on the voltage-sensitive sodium channel, were bound specifically to saturable sites in rainbow trout (Oncorhynchus mykiss) brain synaptoneurosomes.

2. Specific [³H]BTX-B binding was temperature dependent with highest levels of specific [³H]BTX-B binding observed at 7°C. Specific binding was inversely correlated with assay temperature at temperatures above 7°C.

3. Saturating concentrations of scorpion (Leiurus quinquestriatus) venom (ScV) stimulated specific [³H]BTX-B binding at 27°C, but not at 7°C. The dihydropyrazole insecticide RH 3421 inhibited specific [³H]BTX-B binding at 7°C but had no effect on specific binding at 27°C. The sodium channel activators veratridine and aconitine and the local anesthetic dibucaine inhibited specific [³H]BTX-B binding at both 7°C and 27°C.

4. Displacement experiments in the presence of ScV at 27°C gave an equilibrium dissociation constant (K_d) for [³H]BTX-B of 710 nM and a maximal binding capacity (B_max) of 11.3 pmol/mg protein. Kinetic experiments established the rates of association (1.17 × 10⁵min⁻¹ nM⁻¹) and dissociation (0.0514min⁻¹) of the ligand-receptor complex.

5. The binding of [³H]STX reached apparent saturation at 7.5 nM. Scatchard analysis of the saturation data indicated a K_d of 3.8nM and a B_max of 1.9 pmol/mg protein.

6. These studies provide evidence for high affinity, saturable binding sites for [³H]BTX-B and [³H]STX in trout brain preparations. Whereas certain neurotoxins modified the specific binding of [³H]BTX-B in trout brain synaptoneurosomes in a predictable fashion, other compounds known to affect specific [³H]BTX-B binding in mammalian brain preparations had no effect on specific [³H]BTX-B binding in the trout.

1. We have studied the binding characteristics of the hepatic VPRs expressed by rat, cow, pig, sheep and human and have demonstrated species heterogeneity.

2. These species differences are manifested as variation in the VPR capacity (rat > cow > pig > human > sheep), and in the affinity of these receptors for their natural ligand AVP (rat = human > pig = cow).

3. A single class of VPRs, with high affinity for AVP, is present in rat, cow, human and pig liver. In contrast, ovine hepatocytes do not express a VPR.

4. The affinity of the V_1a-selective antagonist d(CH₂)₅Tyr(Me)²AVP is highly dependent on the species utilised, such that rat > human > cow.

1. Subcutaneous injection of vincristine (more than 3 μg) in the catfish, Ictalurus nebulosus, produces a black spot on the skin with a grey surround. Doses between 1 and 3 μg give a less pronounced discolouration.

2. Two to three days after injection of 5 μg vincristine, repetitive activity is detected in primary afferents of unstimulated electroreceptor organs close to the site of injection.

3. Vincristine increases the phase-lag of the modulation of afferent activity in electroreceptor organs during electrical stimulation without a clear effect on the sensitivity of catfish electroreceptor organs.

4. The amplitude of the action potentials of the primary afferents begins to decrease after 2 days; after

3 days they gradually disappear in the background noise.

5. Application of Org 2766, a potentially neurotrophic compound, at 2 days, but not 1 day, before vincristine application prevents vincristine effects on the phase shift.

6. Preliminary electron-microscopical studies of the synapse shows a severe depletion of glycogen granules in the afferent nerve fibre after vincristine application,

7. It is concluded that electroreceptor organs can be used to study neuropathies caused by vincristine, and that Org 2766 may be useful for preventive treatment of such neuropathies.

1. Rainbow trout (Oncorhynchus mykiss) were exposed to a single X-ray dose of 4Gy.

2. The frequency of micronuclei in the peripheral erythrocytes was investigated at regular intervals up to 58 days after the exposure.

3. A flow cytometric method and a semi-automatic image analysis method were used to estimate the micronuclei frequency.

4. The results show that both methods can detect an increased frequency of micronuclei in peripheral erythrocytes from exposed fish.

5. However, the semi-automatic image analysis method was the most stable and sensitive.

1. 4',6-Diamidino-2-phenylindole is a powerful reversible inhibitor of porcine kidney diamine oxidase and partially purified rabbit liver $\text{S-}\text{adenosyl-}\text{L}\text{-methionine}$ decarboxylase.

2. This diamidine has shown to be a competitive inhibitor of porcine kidney diamine oxidase with a Ki value of 13μM.

3. A similar inhibitory pattern has been found on rat liver $\text{S-}\text{adenosyl-}\text{L}\text{-methionine}$ decarboxylase with an estimated Ki of 21 μM.

1. Oreochromis aureus (Steindachner) was exposed to two concentrations of lead and cadmium for 24 hr and 1 week to assess the effects of these pollutants on haematological parameters.

2. Plasma osmolality was found to be the most sensitive blood parameter, affected before other parameters changed.

3. Cadmium appears to be more toxic to O. aureus than lead, having an adverse effect on blood parameters earlier than lead.

4. In the earlier stages of toxicity cadmium appears to have a more pronounced effect on haemoglobin concentration than lead.

5. Cadmium does not depress erythrocyte counts but lead does.

1. Mammary gland of mouse (Mus musculus), rat (Rattus rattus), guinea pig (Cavia porcellus), cow (Bos taurus) and pig (Sus scrofa) contains different but always high concentrations of histamine.

2. Generally, the tissue histamine is localized in mast cells, although non-mast cell histamine immuno-reactivity is also present in mammary glands of the mouse, cow and pig. No histamine immunoreactive nerves could be detected.

3. Mammary glands are able to synthesize and inactivate histamine; the activity of specific histidine decarboxylase and at least one of the catabolizing enzyme could be demonstrated.

4. Histamine fulfils basic criteria for being involved in physiological function of mammary glands.