Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Islet function is regulated by a number of different signals. A main signal is generated by glucose, which stimulates insulin secretion and inhibits glucagon secretion. The glucose effects are modulated by many factors, including hormones, neurotransmitters and nutrients. Several of these factors signal through guanine nucleotide-binding protein (G protein)-coupled receptors (GPCR). Examples of islet GPCR are GPR40 and GPR119, which are GPCR with fatty acids as ligands, the receptors for the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), the receptors for the islet hormones glucagon and somatostatin, the receptors for the classical neurotransmittors acetylcholine (ACh; M(3) muscarinic receptors) and noradrenaline (beta(2)- and alpha(2)-adrenoceptors) and for the neuropeptides pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP; PAC(1) and VPAC(2) receptors), cholecystokinin (CCK(A) receptors) and neuropeptide Y (NPY Y1 receptors). Other islet GPCR are the cannabinoid receptor (CB(1) receptors), the vasopressin receptors (V1(B) receptors) and the purinergic receptors (P(2Y) receptors). The islet GPCR couple mainly to adenylate cyclase and to phospholipase C (PLC). Since important pharmacological strategies for treatment of type 2 diabetes are stimulation of insulin secretion and inhibition of glucagon secretion, islet GPCR are potential drug targets. This review summarizes knowledge on islet GPCR.
 ...
PMID:G-protein-coupled receptors and islet function-implications for treatment of type 2 diabetes. 1790 Jul

Neuropeptides collaborate with conventional neurotransmitters to regulate synaptic output. Pituitary adenylate cyclase-activating polypeptide (PACAP) co-localizes with acetylcholine in presynaptic nerve terminals, is released by stimulation, and enhances nicotinic acetylcholine receptor- (nAChR-) mediated responses. Such findings implicate PACAP in modulating nicotinic neurotransmission, but relevant synaptic mechanisms have not been explored. We show here that PACAP acts via selective high-affinity G-protein coupled receptors (PAC(1)Rs) to enhance transmission at nicotinic synapses on parasympathetic ciliary ganglion (CG) neurons by rapidly and persistently increasing the frequency and amplitude of spontaneous, impulse-dependent nicotinic excitatory postsynaptic currents (sEPSCs). Of the canonical adenylate cyclase (AC) and phospholipase-C (PLC) transduction cascades stimulated by PACAP/PAC(1)R signaling, only AC-generated signals are critical for synaptic modulation since the increases in sEPSC frequency and amplitude were mimicked by 8-Bromo-cAMP, blocked by inhibiting AC or cAMP-dependent protein kinase (PKA), and unaffected by inhibiting PLC. Despite its ability to increase agonist-induced nAChR currents, PACAP failed to influence nAChR-mediated impulse-independent miniature EPSC amplitudes (quantal size). Instead, evoked transmission assays reveal that PACAP/PAC(1)R signaling increased quantal content, indicating that it modulates synaptic function by increasing vesicular ACh release from presynaptic terminals. Lastly, signals generated by the retrograde messenger, nitric oxide- (NO-) are critical for the synaptic modulation since the PACAP-induced increases in spontaneous EPSC frequency, amplitude and quantal content were mimicked by NO donor and absent after inhibiting NO synthase (NOS). These results indicate that PACAP/PAC(1)R activation recruits AC-dependent signaling that stimulates NOS to increase NO production and control presynaptic transmitter output at neuronal nicotinic synapses.
 ...
PMID:PACAP/PAC1R signaling modulates acetylcholine release at neuronal nicotinic synapses. 1995 33

Pituitary adenylate cyclase activating polypeptide (PACAP) is a multifunctional neuropeptide, widely expressed in the nervous system (Vaudry et al., 2009; Starr and Margiotta, 2016). At neuronal synapses where transmission is mediated by nicotinic acetylcholine receptors (nAChRs) transient PACAP exposure increases the frequency and amplitude (FS and AS) of spontaneous excitatory postsynaptic currents (sEPSCs) within minutes. This short-term (ST) plasticity requires high-affinity PACAP receptor (PAC1R) signaling via adenylate cyclase (AC), cyclic AMP (cAMP), Protein kinase A (PKA) and obligatory nAChR-dependent stimulation of nitric oxide (NO) synthesis to retrogradely increase presynaptic ACh release (Pugh et al., 2010; Jayakar et al., 2014). Remarkably, synaptic changes persist 48h after transient PACAP exposure, featuring a similar increase in FS and an even larger increase in AS. Pharmacological studies reveal that this long-term (LT) plasticity requires PACAP/PAC1R signaling via AC and cAMP, but unlike ST plasticity, Phospholipase-C and new gene transcription are also necessary, whereas PKA, nAChR, impulse and NO synthase (NOS1) activities are dispensable. In accord with the increases in FS and AS characterizing LT plasticity, miniature EPSC (mEPSC) frequency, ACh release (quantal content), and mEPSC amplitude (quantal size) all increased in parallel. Consistent with these functional changes, imaging studies reveal that LT, but not ST, PACAP-induced plasticity is accompanied by increases in presynaptic terminal size, postsynaptic nAChR cluster size and density, and the size and density of co-localized pre- and post-synpatic sites. Thus PACAP/PAC1R signaling induces mechanistically distinct forms of synaptic plasticity, with a ST form arising from acute, membrane-delimited processes, and a LT form arising from transcription-dependent alterations in the function and structural arrangement of pre- and post-synaptic components.
 ...
PMID:Pituitary adenylate cyclase activating polypeptide induces long-term, transcription-dependent plasticity and remodeling at autonomic synapses. 2901 14