Neurons second messengers

Polyphosphates and Analogues as Molecular Probes for Neuronal Second Messenger Receptors, Raven Press, NY, 1993, pp 383-416. S. Ozaki, Y. Watanabe, M. Hirata, T. Ogasawara, T. Kanematsu,... 

Metabotropic Those not directly linked to ion channels but initiating biochemical processes that mediate more long-term effects and modify the responsiveness of the neuron. With these the first messenger of synaptic transmission, the NT, activates a second messenger to effect the change in neuron excitability. They are normally associated with reduced membrance conductance and ion flux (unless secondary to... 

The exact process(es) by which a2-adrenoceptors blunt release of transmitter from the terminals is still controversial but a reduction in the synthesis of the second messenger, cAMP, contributes to this process. a2-Adrenoceptors are negatively coupled to adenylyl cyclase, through a Pertussis toxin-sensitive Gi-like protein, and so their activation will reduce the cAMP production which is vital for several stages of the chemical cascade that culminates in vesicular exocytosis (see Chapter 4). The reduction in cAMP also indirectly reduces Ca + influx into the terminal and increases K+ conductance, thereby reducing neuronal excitability (reviewed by Starke 1987). Whichever of these releasecontrolling processes predominates is uncertain but it is likely that their relative importance depends on the type (or location) of the neuron. 

The intracellular processes which precede membrane activation appear to differ from those of MOE neurones, in that cyclic nucleotide gating may not occur. The transduction process which induces current flow in snake VN neurones, utilises as a putative second-messenger the modulator compound inositol triphosphate — Ins. (1,4,5) P3 = IP3 (Liu et al, 1999 Taniguichi et al, 2000). The proposed channel component associated with the microvillous membrane is one of the transient receptor potential family (TRPC-2 Heading Fig., pp. 94), the p-splice... 

Iida A. and Kashiwayanagi M. (2000). Responses to putative second messengers and odorants in water nose olfactory neurons of Xenopus laevis. Chem Senses 25, 55-59. 

Gopalakrishnan, M., Molinari, E., Sullivan, J. Regulation of human 0 ,P2 neuronal nicotinic acetylcholine receptors by cholinergic channel ligands and second messenger pathways. Mol. Pharmacol. 52 524, 1997. 

The first two antidepressants, iproniazid and imipramine, were developed in the same decade. They were shown to reverse the behavioural and neurochemical effects of reserpine in laboratory rodents, by inhibiting the inactivation of these monoamine transmitters (Leonard, 1985). Iproniazid inhibits MAO (monoamine oxidase), an enzyme located in the presynaptic neuronal terminal which breaks down NA, 5-HT and dopamine into physiologically inactive metabolites. Imipramine inhibits the reuptake of NA and 5-HT from the synaptic cleft by their transporters. Therefore, both of these drugs increase the availability of NA and 5-HT for binding to postsynaptic receptors and, therefore, result in enhanced synaptic transmission. Conversely, lithium, the oldest but still most frequently used mood stabiliser (see below), decreases synaptic NA (and possibly 5-HT) activity, by stimulating their reuptake and reducing the availability of precursor chemicals required in the biosynthesis of second messengers. 

Over the last four decades, cAMP has been shown to serve as an intracellular second messenger for numerous extracellular signals in the nervous system. In fact, the number of functional processes regulated by cAMP is too large to enumerate here in detail. It is important, however, to review the general types of effects that cAMP exerts in neurons. 

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