Comparative biochemistry and physiology. C, Comparative pharmacology and toxicology最新文献

1. Effects of Ca2+ agonist and antagonists on cytosolic free Ca2+ concentration [( Ca2+]i)were studied using quin2. 2. Nicardipine (NIC), diltiazem (DIL) and verapamil (VER) had no effect on the rise in [Ca2+]i evoked by carbachol. Methoxamine-elevated [Ca2+]i was inhibited by VER but not by NIC and DIL. 3. All Ca2+ antagonists tested produced a decline of [Ca2+]i elevated by isoproterenol to the resting level. 4. The addition of 30 mM K+ gradually elevated [Ca2+]i in normal and Ca2+-free media, but it did not increase 45Ca2+ uptake into cells. BAY K 8644 did not increase [Ca2+]i. 5. We suggest that voltage-sensitive Ca2+ channels are lacking and that at least 2 distinct receptor-operated Ca2+ channels exist in rat parotid cells.

Forskolin, a stimulator of adenylate cyclase, induced a dose-dependent and reversible dispersion of pigment within fish leucophores. Li+, known as an inhibitor of the enzyme, depressed pigment-dispersion response of leucophores to either forskolin or isoproterenol, inducing an aggregation of pigment within the cells. These results indicate that Li+ acted on the cells through inhibition of forskolin- or isoproterenol-stimulated adenylate cyclase activity. The results suggest that adenylate cyclase is involved in the pigment-dispersion response of leucophores and that cAMP acts as a second messenger in the response.

Effects of cyclic nucleotides on motile iridophores were examined in the blue damselfish, Chrysiptera cyanea. All of the cyclic nucleotides tested, i.e. cAMP, 2',3'-cAMP and cGMP, accelerated the clearing response of the cells even at concentrations of 10(-5) or 10(-4) M. The action of these nucleotides was effectively antagonized by methylxanthines. These results suggest that the effect of cyclic nucleotides on damselfish iridophores is mediated by adenosine receptors in a similar fashion to the action of adenosine.

Using the medaka, Oryzias latipes (orange-red variety), the mechanisms of action on leucophores of adenosine and adenine nucleotides, including cyclic AMP, were studied. All these substances were found to be very effective in dispersing leucosomes. Their pigment-dispersing action was antagonized by methylxanthines. These substances did not aggregate leucosomes. It was concluded that leucophores possess specific binding sites for adenosine, i.e. adenosine receptors, on the cell membrane, which mediate leucosome dispersion. Further, it was shown that even the action of an established intracellular second messenger, cyclic AMP, is primarily manifested through the receptors.

Morphological and pharmacological investigations were made of two giant neurons, RPeNLN (right pedal nerve large neuron) and LPeNLN (left pedal nerve large neuron), situated symmetrically on the anterior surface of the pedal ganglia of an African giant snail (Achatina fulica Férussac). The two neurons (about 250-300 microns in diameter) were the largest ones identified in the ganglia of the snail species. The axonal pathways of the two neurons were symmetrical; of their four main axonal branches, the three main branches innervated the ipsilateral pedal nerves, whereas the last main branch projected to the contralateral pedal nerves. The pharmacological features of the two neurons were very similar. Both were inhibited markedly by dopamine [minimum effective concentrations (MECs): 3 X 10(-6)-10(-5) M], DL-octopamine (MECs: 2 X 10(-6)-2 X 10(-5) M), 5-hydroxytryptamine (MEC: 3 X 10(-6) M), GABA (MEC: 3 X 10(-4) M), L-homocysteic acid (MECs: 3 X 10(-5)-10(-4) M) and erythro-beta-hydroxy-L-glutamic acid (MEC: 3 X 10(-5) M). Acetylcholine showed varied effects, either excitatory or inhibitory, on the two neurons examined. No substances were found to have any marked excitatory effects on the neurons.

The types of innervation to integumental melanophores were surveyed comparatively within the order Siluriformes. In fish or many families, pigment aggregation within melanophores was found to be under the control of adrenergic sympathetic postganglionic fibers as in other fish. In silurid catfish, on the other hand, the cells were found to be regulated cholinergically, though the fibers concerned were sympathetic postganglionic. Muscarinic cholinoceptors mediate the melanin-aggregating response. In some catfish belonging to Bagridae, Pimelodidae and Callichthyidae, the melanophores strangely possessed cholinoceptors, notwithstanding the fact that they were under adrenergic nervous control. These results were discussed in conjunction with the phylogeny of Siluriformes.

Relaxation in response to electrical stimulation has been studied in isolated tail arteries from rats, cats and pigs. Electrical stimulation elicited contractile responses in unstimulated strips, but caused frequency-dependent relaxations in tail arteries from all species studied, following contractile responses by various agents. The order of susceptibility to the relaxant effect of electrical stimulation in arteries from all three species was pig greater than cat greater than rat. Relaxations to electrical stimulation were unaffected by prior treatment of arteries with atropine, propranolol, tetrodotoxin, indomethacin, ouabain, pyrilamine and chemical denervation with 6-hydroxy-dopamine, but were prevented, dose-dependently, by cimetidine and aminophylline (antagonists of histamine H2-receptor and adenosine P1-receptor, respectively). The results suggest that relaxation of tail arteries from the rat, cat and pig in response to electrical stimulation is modulated by histamine and adenosine.

The influence of Ca-antagonists and antispasmodic drugs on contractions by ACh and by DMPP were investigated. Verapamil (10(-5) to 10(-4) M), diltiazem (10(-5) to 10(-4) M) and D-600 (10(-5) to 10(-4) M) depressed both the contractions in a dose dependent manner. Papaverine (10(-5) to 10(-4) M) and Aspaminol (10(-6) to 10(-5) M) also depressed both the contractions in a dose dependent manner. These findings indicate that Ca2+, which initiates the contraction by ACh, is supplied from both the external medium and intracellular store sites.

Two giant neurons, d-RCDN (dorsal-right cerebral distinct neuron) and d-LCDN (dorsal left cerebral distinct neuron), with a diameter of about 100 microns, were found symmetrically on the dorsal surface of the cerebral ganglia of an African giant snail (Achatina fulica Férussac). They showed spontaneous spike discharges at a stable frequency. Two giant neurons, v-RCDN (ventral-right cerebral distinct neuron) and v-LCDN (ventral-left cerebral distinct neuron), (diameter, approx. 150 microns) were identified on the ventral surface of the same ganglia. No spontaneous spike discharges were evident. Both d-RCDN and d-LCDN were equally inhibited by dopamine, octopamine, 5-hydroxytryptamine and histamine. Acetylcholine sometimes showed inhibitory effects, but they were not so stable. No substance having excitatory effects on the neurons was found. Both v-RCDN and v-LCDN were equally excited by octopamine, 5-hydroxytryptamine, GABA and acetylcholine and inhibited by dopamine and beta-hydroxy-L-glutamic acid.