PT  - JOURNAL ARTICLE
AU  - N C Schaad
AU  - J Vanecek
AU  - I R Rodriguez
AU  - D C Klein
AU  - L Holtzclaw
AU  - J T Russell
TI  - Vasoactive intestinal peptide elevates pinealocyte intracellular calcium concentrations by enhancing influx: evidence for involvement of a cyclic GMP-dependent mechanism.
DP  - 1995 May 01
TA  - Molecular Pharmacology
PG  - 923--933
VI  - 47
IP  - 5
4099  - http://molpharm.aspetjournals.org/content/47/5/923.short
4100  - http://molpharm.aspetjournals.org/content/47/5/923.full
SO  - Mol Pharmacol1995 May 01; 47
AB  - Vasoactive intestinal peptide (VIP) receptor density is high in the pineal gland, which receives VIP innervation and responds to VIP with a relatively small increase in cAMP and cGMP levels. In the present study, we show that VIP (5-200 nM) treatment increased the intracellular calcium concentration ([Ca2+]i) in 64% of isolated individual pinealocytes; in comparison, norepinephrine (NE) elevated [Ca2+]i in 93% of the cells and produced more robust responses. Analysis of the role of second messengers indicated that [Ca2+]i was strongly elevated by cGMP analogs, but not by cAMP analogs. The nitric oxide-releasing agent S-nitro-N-acetylpenicillamine and 2,2-diethyl-1-nitroxyhydraxine also elevated [Ca2+]i. Investigation of the mechanisms revealed that responses to VIP or 8-bromo-cGMP involved Ca2+ influx, as did the plateau component of the response to NE; the large rapid component of the response to NE, however, appeared to reflect release from intracellular stores. Pharmacological studies indicated that the VIP-induced Ca2+ influx was mediated by a retinal rod-type cyclic nucleotidegated cation channel, expression of which was confirmed by reverse transcription-polymerase chain reaction analysis. These observations indicate that fundamentally different mechanisms generate the responses to NE and VIP. The dominant effect of VIP causing transient elevation of [Ca2+]i appears to be through cGMP gating aI-cis-diltiazem-sensitive rod-type cyclic nucleotide-gated cation channel. In contrast, the dominant effect of NE on [Ca2+]i is due to enhanced Ca2+ release from intracellular stores; the plateau component is due to influx through aI-cis-diltiazem-insensitive channel.