‘TRPing’ Synaptic Ribbon Function in the Rat Pineal Gland: Neuroendocrine Regulation Involves the Capsaicin Receptor TRPV1

Abstract

Synaptic ribbons (SRs) are presynaptic structures thought to regulate and facilitate multivesicular release. In the pineal gland, they display a circadian rhythm with higher levels at night paralleling melatonin synthesis. To gain more insight into the processes involved and the possible functions of these structures, a series of experiments were conducted in rodents. We studied the regional distribution of a molecular marker of pineal SRs, the kinesin motor KIF3A in the gland. Respective immunoreactivity was abundant in central regions of the gland where sympathetic fibers were less dense, and vice versa, revealing that intercellular communication between adjacent pinealocytes is enhanced under low sympathetic influence. KIF3A was found to be colocalized to the transient receptor potential channel of the vanilloid receptor family, subtype 1 (TRPV1). The TRPV1 agonist capsaicin increased melatonin secretion from perifused pineals in a dose-dependent manner that was blocked by the competitive TRPV1 antagonist capsazepine. No change in free intracellular calcium was observed in response to TRPV1 ligands applied to pinealocytes responding to norepinephrine, bradykinin and/or depolarization. These data clearly indicate that TRPV1 actively regulates pineal gland function.

Role of melatonin on calcium signaling and mitochondrial oxidativestress in epilepsy: focus on TRP channels

“…The neuroendocrine modulator role and the regional distribution of a molecular marker of pineal synaptic ribbons in the pineal gland of rodents were investigated by Reuss et al (2010). They observed that the TRPV1 stimulator capsaicin increased melatonin secretion from perfused pineal glands in a dose-dependent manner that was blocked by the TRPV1 blocker capsazepine (CPZ).…”

“…Intracellular ROS are scavenged by melatonin and its metabolites (Espino et al, 2012;Bejarano et al, 2014). Melatonin has been reported to modulate the L-type voltage-gated calcium channel (VGCC) channelopathies (Lee et al, 2006;Nazıroğlu, 2009;Choi et al, 2014), oxidative stress-activated TRPV1 and TRPM2 channels (Reuss et al, 2010;Nazıroğlu et al, 2012a), and glutamate receptors (Molina-Carballo et al, 2007). It is well known that the GABA neurotransmitter has an important role in the induction of epilepsy.…”

Mass‐spectrometry analysis of the human pineal proteome during night and day and in autism

“…17,18 The synaptic ribbons are electron-dense structures tethering synaptic vesicles, considered as specific marker structure for the pinealocytes with a unique type of chemical synapse, referred by Jouvet et al (1994) as the ribbon synapse. [19][20][21][22][23] The ribbon synapse is not a classical synapse and its protein composition differs from conventional synapses reflecting different modes of transmitter release. In contrast to other synapses, there is no postsynaptic specialization in apposition to the ribbon and vesicles.…”

“…The main cell type of the mammalian pineal parenchymal is the pinealocyte, (~95%), however, many endothelial and vascular smooth muscle cells, few glia, phagocytic cells, and rarely neurons are present, too 17,18 . The synaptic ribbons are electron‐dense structures tethering synaptic vesicles, considered as specific marker structure for the pinealocytes with a unique type of chemical synapse, referred by Jouvet et al (1994) as the ribbon synapse 19‐23 . The ribbon synapse is not a classical synapse and its protein composition differs from conventional synapses reflecting different modes of transmitter release.…”

Modulation of Ca2+ oscillation and melatonin secretion by BKCa channel activity in rat pinealocytes

“…These Ca 2ϩ oscillations are mediated by Ca 2ϩ influx through VDCCs and involved in the inhibitory mechanism of melatonin secretion, which is known to be regulated by the parasympathetic activity in mammalian pineal glands. In addition to VDCCs (1,9,22,40), molecular and functional expressions of voltage-dependent K ϩ channels (1,4,7,8), nonselective cation channels (12,29), store-operated Ca 2ϩ channels (21), and cyclic nucleotide-gated channels (32) have been suggested in mammalian pineal glands. Furthermore, membrane currents presumably due to the large-conductance Ca 2ϩ -activated K ϩ (BK Ca ; also known as K Ca 1.1) channel activation have been recorded in mammalian pinealocytes (7,8,21,22).…”