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Physiological and pharmacological modulation of postreceptor signals
Pharmacological Research. Vol. 22. Supplement 2.1990
79
PHYSIOLOGICAL AND PHARMACOLOGICAL MODULATION OF POSTRECEPTOR SIGNALS. P.L. Canonico. Institute of pharmacology, University of catania School of Medicine, catania, Italy. The efficiency of receptor-coupled signal trans duct ion is finely regulated by the duration of exposure to selective agonists as well as by a variety of ionic or organic modulators. It is well known that a rapid and transient repetitive exposure to agonists leads to receptor facilitation, whereas continuous exposure results in receptor desensitization. The latter mechanism may be involved in the long-lasting changes in receptor sensitivity that occur in the postnatal life during synaptic formation. Receptor desensitization has been investigated in details by measuring activation of adenylate cyclase or phosphoinositide CPPI) hydrolysis in response to specific agonists. We have focused on metabotropic glutamate receptors coupled to PPI hydrolysis. In neuronal cultures, these receptors undergo rapid and long-lasting desensitization that, on a quantitative basis, is greater than desensitization of muscarinic receptors. This process involves, in its rapid component, activation of protein kinase C, and is specific for the different receptor subtypes. Phosphorylation of a specific GTP-binding protein by protein kinase C may contribute to the dramatic changes in the sensitivity of metabotropic glutamate receptors during development. The efficiency of signal transducing mechanisms may be also modulated by regulatory molecules either produced in the central nervous system or at endocrine level. Among these, TRH potentiates signal transduction at a specific NMDA receptor subtype coupled to PPI hydrolysis. This mechanism may underlie the neurotrophic activity of TRH in cultured neurons. Steroid hormones may also modulate signal transduction, as reflected by the action of some progesterone derivatives at the GABA A receptor ionophore complex, as well as by the sex- and region-dependent regulation of a,-adrenergic and muscarinic receptor-mediated PPI hydrolysis by gonadal hormones.
1043--6618/90/22110079--01/$03.00/0
© 1990The Italian Pharmacological Society
79
PHYSIOLOGICAL AND PHARMACOLOGICAL MODULATION OF POSTRECEPTOR SIGNALS. P.L. Canonico. Institute of pharmacology, University of catania School of Medicine, catania, Italy. The efficiency of receptor-coupled signal trans duct ion is finely regulated by the duration of exposure to selective agonists as well as by a variety of ionic or organic modulators. It is well known that a rapid and transient repetitive exposure to agonists leads to receptor facilitation, whereas continuous exposure results in receptor desensitization. The latter mechanism may be involved in the long-lasting changes in receptor sensitivity that occur in the postnatal life during synaptic formation. Receptor desensitization has been investigated in details by measuring activation of adenylate cyclase or phosphoinositide CPPI) hydrolysis in response to specific agonists. We have focused on metabotropic glutamate receptors coupled to PPI hydrolysis. In neuronal cultures, these receptors undergo rapid and long-lasting desensitization that, on a quantitative basis, is greater than desensitization of muscarinic receptors. This process involves, in its rapid component, activation of protein kinase C, and is specific for the different receptor subtypes. Phosphorylation of a specific GTP-binding protein by protein kinase C may contribute to the dramatic changes in the sensitivity of metabotropic glutamate receptors during development. The efficiency of signal transducing mechanisms may be also modulated by regulatory molecules either produced in the central nervous system or at endocrine level. Among these, TRH potentiates signal transduction at a specific NMDA receptor subtype coupled to PPI hydrolysis. This mechanism may underlie the neurotrophic activity of TRH in cultured neurons. Steroid hormones may also modulate signal transduction, as reflected by the action of some progesterone derivatives at the GABA A receptor ionophore complex, as well as by the sex- and region-dependent regulation of a,-adrenergic and muscarinic receptor-mediated PPI hydrolysis by gonadal hormones.
1043--6618/90/22110079--01/$03.00/0
© 1990The Italian Pharmacological Society