Heterogenity of pituitary adenylate cyclase activating polypeptide and vasoactive intestinal polypeptide receptors in rat intrinsic cardiac neurons

University of South Florida, Tampa, Florida, United States
Neuroscience Letters (Impact Factor: 2.03). 09/2002; 328(1):45-9. DOI: 10.1016/S0304-3940(02)00445-7
Source: PubMed


The expression of receptors for pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) was investigated in isolated parasympathetic neurons of neonatal rat intracardiac ganglia using single-cell reverse transcription-polymerase chain reaction. Individual neurons were shown to express multiple isoforms of the PACAP receptor, PAC1, including PAC1-short, -HOP1 and -HOP2 variants, which differ in the region encoding the G protein-binding domain. The PAC1-HOP1 isoform was the predominant species, being expressed at higher levels and in a greater number of cells than other PAC1 variants. In addition to PAC1, intrinsic cardiac neurons express transcripts for the VIP receptors, VPAC1 and VPAC2, with VPAC2 being found in a greater proportion of the neurons. These findings may explain the complex effects of PACAP and VIP on neuroexcitability in mammalian intracardiac ganglia.

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    • "Braas et al. (1998) showed that adult guinea pig intracardiac neurons express the PAC 1 receptor. More recently, DeHaven and Cuevas (2002) reported that dissociated neonatal rat intracardiac neurons can express both PAC 1 and VPAC receptors. Based on the electrophysiological results, Braas et al. (1998) postulated that the PACAP-induced increase in excitability in adult guinea pig intracardiac neurons is mediated by PAC 1 receptors because PACAP was more effective than VIP. "
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    ABSTRACT: Mechanisms modulating the pituitary adenylate cyclase activating polypeptide (PACAP)-induced increase in excitability have been studied using dissociated guinea pig intrinsic cardiac neurons and intact ganglion preparations. Measurements of intracellular calcium (Ca2+) with the fluorescent Ca2+ indicator dye fluo-3 indicated that neither PACAP nor vasoactive intestinal polypeptide (VIP) at either 100 nM or 1 microM produced a discernible elevation of intracellular Ca2+ in dissociated intracardiac neurons. For neurons in ganglion whole mount preparations kept in control bath solution, local application of PACAP significantly increased excitability, as indicated by the number of action potentials generated by long depolarizing current pulses. However, in a Ca2+ -deficient solution in which external Ca2+ was replaced by Mg2+ or when cells were bathed in control solution containing 200 microM Cd2+, PACAP did not enhance action potential firing. In contrast, in a Ca2+ -deficient solution with Ca2+ replaced by strontium (Sr2+), PACAP increased excitability. PACAP increased excitability in cells treated with a combination of 20 microM ryanodine and 10 mM caffeine to interrupt release of Ca2+ from internal stores. Experiments using fluo-3 showed that ryanodine/caffeine pretreatment eliminated subsequent caffeine-induced Ca2+ release from intracellular stores, whereas exposure to the Ca2+ -deficient solution did not. In dissociated intracardiac neurons voltage clamped with the perforated patch recording technique, 100 nM PACAP decreased the voltage-dependent barium current (IBa). These results show that, in the guinea pig intracardiac neurons, the PACAP-induced increase in excitability apparently requires Ca2+ influx through Cd2+ -sensitive calcium permeable channels other than voltage-dependent Ca2+ channels, but not Ca2+ release from internal stores.
    Journal of Neurophysiology 05/2006; 95(4):2134-42. DOI:10.1152/jn.01077.2005 · 2.89 Impact Factor

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    ABSTRACT: Autonomic control of cardiac function depends on the coordinated activity generated by neurons within the intracardiac ganglia, and intrinsic feedback loops within the ganglia provide precise control of cardiac function. Both pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are important regulators of cell-to-cell signaling within the intracardiac ganglia, and PACAP and VIP action on these ganglia, mediated through associated receptors, play an important role in the regulation of coronary blood flow, cardiac contraction, relaxation, and heart rate. Results reported here using PACAP and VIP provide direct evidence of some of the complex signaling which occurs in neurons of the rat intracardiac ganglia.
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