The Journal of comparative neurology
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Calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) comprise a receptor for calcitonin gene related peptide (CGRP) and intermedin. Although CGRP is widely expressed in the nervous system, less is known about the localization of CLR and RAMP1. To localize these proteins, we raised antibodies to CLR and RAMP1. ⋯ Nerve fibers containing CGRP and intermedin were closely associated with CLR fibers in the gastrointestinal tract and dorsal horn, and CGRP and CLR colocalized in DRG neurons. Thus, CLR and RAMP1 may mediate the effects of CGRP and intermedin in the nervous system. However, mRNA encoding RAMP2 and RAMP3 was also detected in the gastrointestinal tract, DRG, and dorsal horn, suggesting that CLR may associate with other RAMPs in these tissues to form a receptor for additional peptides such as adrenomedullin.
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Comparative Study
Nerve growth factor sensitivity is broadly distributed among myenteric neurons of the rat colon.
Nerve growth factor (NGF) acts on the two-receptor system of trkA and p75 to mediate neuroprotection and influence phenotype and function in the peripheral nervous system, but the effects of NGF on the enteric nervous system (ENS) are virtually unknown. To establish a basis for enteric responsiveness to NGF, we studied the presence and distribution of NGF-sensitive receptors in the myenteric neurons of the normal rat colon and examined their activation via trkA phosphorylation. ⋯ More thanr 60% of the myenteric neurons expressed both receptors, and exogenous application of NGF resulted in trkA phosphorylation, evidence for high NGF sensitivity within the ENS. trkA was co-expressed with choline acetyltransferase (61% of trkA-positive neurons), neuronal nitric oxide synthase (22%), or calbindin (10%), suggesting widespread potential for NGF action. We conclude that functional receptors for NGF are widely distributed among the diverse enteric phenotypes and argue for a novel NGF-mediated regulatory system within the ENS.
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Microinjection of pentobarbital and GABA(A)-receptor agonists into a brainstem region we have called the mesopontine tegmental anesthesia area (MPTA; Devor and Zalkind [2001] Pain 94:101-112) induces a general anesthesia-like state. As in systemic general anesthesia, rats show loss of the righting reflex, atonia, nonresponsiveness to noxious stimuli, and apparent loss of consciousness. GABA(A) agonist anesthetics acting on the MPTA might suppress movement by engaging endogenous motor regulatory systems previously identified in research on decerebrate rigidity and REM sleep atonia. ⋯ Projections are bilateral with an ipsilateral predominance. We propose that GABA(A) agonist anesthetics induce immobility at least in part by acting on these endogenous motor control pathways via the MPTA. Analysis of MPTA connectivity has the potential for furthering our understanding of the neural circuitry responsible for the various functional components of general anesthesia.