The pituitary adenylate cyclase‐activating polypeptide modulates glutamatergic calcium signalling: investigations on rat suprachiasmatic nucleus neurons

• Published in: Journal of neurochemistry 2001-10, Vol.79 (1), p.161-171
• Main Authors: Kopp, Michael D. A., Meissl, Hilmar, Dehghani, Faramarz, Korf, Horst‐Werner
• Format: Article
• Language: English
• Subjects: alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - metabolism; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - pharmacology; AMPA; Animals; Biological and medical sciences; Calcium - metabolism; Cells, Cultured; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Cyclic AMP - pharmacology; Drug Interactions; Fluorescent Dyes; Fundamental and applied biological sciences. Psychology; Fura-2; glutamate; Glutamic Acid - pharmacology; Glutamic Acid - physiology; kainate; metabotropic glutamate receptors; N-Methylaspartate - physiology; Neurons - drug effects; Neurons - metabolism; Neuropeptides - pharmacology; NMDA; PACAP; Pituitary Adenylate Cyclase-Activating Polypeptide; Rats; Rats, Wistar; Receptors, Glutamate - drug effects; Receptors, Glutamate - physiology; Receptors, Kainic Acid - drug effects; Receptors, Kainic Acid - physiology; Receptors, Metabotropic Glutamate - drug effects; Receptors, Metabotropic Glutamate - physiology; Receptors, N-Methyl-D-Aspartate - drug effects; Receptors, N-Methyl-D-Aspartate - physiology; Signal Transduction - drug effects; Suprachiasmatic Nucleus - cytology; Vertebrates: nervous system and sense organs
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2001.00553.x

Circadian rhythms generated by the hypothalamic suprachiasmatic nucleus (SCN) are synchronized with the external light/dark cycle by photic information transmitted directly from the retina via the retinohypothalamic tract (RHT). The RHT contains the neurotransmitters glutamate and pituitary adenylate cyclase‐activating polypeptide (PACAP), which code chemically for ‘light’ or ‘darkness’ information, respectively. We investigated interactions of PACAP and glutamate by analysing effects on the second messenger calcium in individual SCN neurons using the Fura‐2 technique. PACAP did not affect NMDA‐mediated calcium increases, but influenced signalling cascades of non‐NMDA glutamate receptors, which in turn can regulate NMDA receptors. On the one hand, PACAP amplified/induced glutamate‐dependent calcium increases by interacting with α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA)/kainate signalling. This was not related to direct PACAPergic effects on the second messengers cAMP and calcium. On the other hand, PACAP reduced/inhibited calcium increases elicited by glutamate acting on metabotropic receptors. cAMP analogues mimicked this inhibition. Most neurons displaying PACAPergic neuromodulation were immunoreactive for vasoactive intestinal polypeptide, which is a marker for retinorecipient SCN neurons. The observed PACAPergic effects provide a broad range of interactions that allow a fine‐tuning of the endogenous clock by the integration of ‘light’ and ‘darkness’ information on the level of single SCN neurons.