1 2-(Carboxycyclopropyl)glycines (CCGs) are conformationally restricted glutamate analogues and consist of eight isomers including L-and D-forms. The agonist potencies and selectivities of these compounds for metabotropic glutamate receptors (mGluRs) were studied by examining their effects on the signal transduction of representative mGluRl, mGluR2 and mGluR4 subtypes in Chinese hamster ovary cells expressing the individual cloned receptors. 2 Two extended isomers of L-CCG, L-CCG-I and L-CCG-II, effectively stimulated phosphatidylinositol hydrolysis in mGluR1-expressing cells. The rank order of potencies of these compounds was Lglutamate > L-CCG-I > L-CCG-II. 3 L-CCG-I and L-CCG-II were effective in inhibiting the forskolin-stimulated adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation in mGluR2-expressing cells. Particularly, L-CCG-I was a potent agonist for mGluR2 with an EC50 value of 3 x IO-' M, which was more than an order of potency greater than that of L-glutamate. 4 L-CCG-I evoked an inhibition of the forskolin-stimulated cyclic AMP production characteristic of mGluR4 with a potency comparable to L-glutamate. 5 In contrast to the above compounds, the other CCG isomers showed no appreciable effects on the signal transduction involved in the three mGluR subtypes. 6 This investigation demonstrates not only the importance of a particular isomeric structure of CCGs in the interaction with the mGluRs but also a clear receptor subtype specificity for the CCG-receptor interaction, and indicates that the CCG isomers would serve as useful agonists for investigation of functions of the mGluR family.
Neuropharmacological actions of a novel metabotropic glutamate receptor agonist, (2S,1′R,2′R,3′R)‐2‐(2,3‐dicarboxycyclopropyl)glycine (DCG‐IV), were examined in the isolated spinal cord of the newborn rat, and compared with those of the established agonists of (2S,1′S,2′S)‐2‐(carboxycyclopropyl)glycine (l‐CCG‐I) or (1S,3R)‐1‐aminocyclopentane‐1,3‐dicarboxylic acid ((1S,3R)‐ACPD).
At concentrations higher than 10 μm, DCG‐IV caused a depolarization which was completely blocked by selective N‐methyl‐d‐aspartate (NMDA) antagonists. The depolarization was pharmacologically quite different from that caused by l‐CCG‐I and (1S,3R)‐ACPD.
DCG‐IV reduced the monosynaptic excitation of motoneurones rather than polysynaptic discharges in the nanomolar range without causing postsynaptic depolarization of motoneurones. DCG‐IV was more effective than l‐CCG‐I, (1S,3R)‐ACPD or l‐2‐amino‐4‐phosphonobutanoic acid (l‐AP4) in reducing the monosynaptic excitation of motoneurones.
DCG‐IV (30 nm–1 μm) did not depress the depolarization induced by known excitatory amino acids in the newborn rat motoneurones, but depressed the baseline fluctuation of the potential derived from ventral roots. Therefore, DCG‐IV seems to reduce preferentially transmitter release from primary afferent nerve terminals.
Depression of monosynaptic excitation caused by DCG‐IV was not affected by any known pharmacological agents, including 2‐amino‐3‐phosphonopropanoic acid (AP3), diazepam, 2‐hydroxysaclofen, picrotoxin and strychnine.
DCG‐IV has the potential of providing further useful information on the physiological function of metabotropic glutamate receptors.
The structure of the juvenile hormone (JH) in the suborder Heteroptera, order Hemiptera, has been known for a very long time to be different from the JH of other orders, but the structure has been a matter of controversy. The structure was first elucidated by an unprecedented approach involving the screening of a JH molecular library. The novel Heteroptera-specific JH (JHSB3) is a new category of JH that is featured by the skipped bisepoxide structure.
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