Spinal cord subtypes

Three tachykinin GPCRs, NK, NK, and NK, have been identified and cloned. AH are coupled to phosphatidjhnositol hydrolysis. The NK receptor is selective for substance P (SP) and is relatively abundant in the brain, spinal cord, and peripheral tissues. The NK receptor is selective for NKA and is present in the gastrointestinal tract, urinary bladder, and adrenal gland but is low or absent in the CNS. The NIC receptor is selective for NKB and is present in low amounts in the gastrointestinal tract and urinary bladder, but is abundant in some areas of the CNS, ie, the spinal dorsal bom, soUtary nucleus, and laminae IV and V of the cortex with moderate amounts in the interpeduncular nucleus. Mismatches in the distribution of the tachykinins and tachykinin receptors suggest the possibility of additional tachykinin receptor subtypes. 

Morales, M., Battenberg, E. Bloom, F. E. (1998). Distribution of neurons expressing immunoreactivity for the 5-HT3 receptor subtype in the rat brain and spinal cord. J. Comp. Neurol. 402, 385-401. 

Ensini, M., Tsuchida, T. M., Belting, H.-G. and Jessell, T. M. The control of rostrocaudal pattern in the developing spinal cord specification of motor neuron subtype identity is initiated by signals from paraxial mesoderm. Development 125 969-982,1998. 

Bohlhalter, S., Weinmann, O., Mohler, H., and Fritschy, J. M. (1996) Laminar compart-mentalization of GABAA-receptor subtypes in the spinal cord../. Neurosci. 16,283-297. 

Zolpidem (1) is an effective hypnotic agent indicated for the short-term treatment of insomnia. Zolpidem interacts with the GABAa receptor, and its pharmacological effect is blocked by the benzodiazepine-receptor antagonist fiumazenil (Sanger and Depoortere, 1998). Zolpidem displaces benzodiazepines more selectively from the cerebellum than the hippocampus or spinal cord, consistent with preferential interaction with the ajGABAA receptor subtype (sometimes referred to as the benzodiazepine coi receptor). Studies... 

Receptors containing the ai, a2, a3 or as subunit in combination with any of the P-subimits and the y2 subunit are most prevalent in the brain (Fig. 3). These receptors are sensitive to benzodiazepine modulation. The major receptor subtype is assembled from the subunits aiP2Y2. with only a few brain regions lacking this receptor (granule cell layer of the olfactory bulb, reticular nucleus of the thalamus, spinal cord motoneurons) (Fritschy and Mohler 1995 Pirker et al. 2000 Fritschy and Brunig 2003) (Table 1). 

Bohlhalter S, Weinmann O, Mdhler H, Fritschy JM (1996) Laminar compartmentalization of GABAA-receptor subtypes in the spinal cord an immunohistochemical study. J Nemosci... 

There is good evidence that the facilitation of peripheral sympathetic nervous system transmission prcxluced by the amphetamines also occurs in the CNS.The possibihty that amphetamines act indirectly (i.e., by releasing monoamines) at monoaminergic synapses in the brain and spinal cord seems likely. However, amphetamine has effects beyond displacement of catecholamines these include inhibition of neuronal amine uptake, direct stimulation of dopamine and serotonin receptors, antagonism of catecholamine action at certain subtypes of adrenoceptors, and inhibition of monoamine oxidase. Interestingly, none of these actions explains the therapeutic benefit of the amphetamines in hyperkinetic children. 

In the spinal cord, a2-agonists act on receptors located on the terminals of primary afferent fibers in the dorsal horn substantia gelatinosa to reduce nociceptive transmission by inhibiting the release of glutamate and substance P (Collin et al., 1994 Hamalainen and Pertovaara, 1995) (see Fig. 2). These receptors appear to be primarily of the a2A subtype which is negatively coupled to adenylate cyclase (Lakhlani et al., 1997 see Millan, 1999 but see Sawamura et al., 2000, and references therein for a discussion of the possible involvement of other a2-receptor subtypes in antinociception). Like activation of p-opioid receptors, the activation of a2-receptors increases the potassium conductance of the cells bearing these receptors, thus reducing cellular excitability. 

Naguib, M. and Yaksh, T.L. Characterization of muscarinic receptor subtypes that mediate antinociception in the rat spinal cord, Anesth. Analg. 1997, 85, 847-853. 

Bonanno G, Raiteri M (1993a) Multiple GABAb receptors. Trends Pharmacol Sci 14 259-61 Bonanno G, Raiteri M (1993b) Gamma-aminobutyric (GABA) autoreceptors in rat cerebral cortex and spinal cord represent pharmacologically distinct subtypes of the GABAb receptor. J Pharmacol Exp Ther 265 765-70... 

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