Properties and distribution of receptors for pituitary adenylate cyclase activating peptide (PACAP) in rat brain and spinal cord

Cauvin, Annick; Robberecht, Patrick; Neef, Philippe De; Gourlet, Philippe; Vandermeers, André; Vandermeers‐Piret, Marie‐Claire; Christophe, Jean

doi:10.1016/0167-0115(91)90478-y

Cited by 91 publications

(33 citation statements)

References 19 publications

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“…PACAP (6 -38) is an antagonist specific for the PAC1 receptor, which is the predominant form in the central nervous system (5,25) but also acts at the VPAC2 receptor, albeit with a 10-fold lesser affinity (7,20,45). PACAP(6 -38) Fig.…”

Section: Discussionmentioning

confidence: 99%

Intrathecal PACAP-38 causes increases in sympathetic nerve activity and heart rate but not blood pressure in the spontaneously hypertensive rat

Farnham

Inglott

Pilowsky

2011

American Journal of Physiology-Heart and Circulatory Physiology

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Farnham MM, Inglott MA, Pilowsky PM. Intrathecal PACAP-38 causes increases in sympathetic nerve activity and heart rate but not blood pressure in the spontaneously hypertensive rat. Am J Physiol Heart Circ Physiol 300: H214 -H222, 2011. First published October 15, 2010 doi:10.1152/ajpheart.00662.2010.-The rostral ventrolateral medulla contains presympathetic neurons that project monosynaptically to sympathetic preganglionic neurons (SPN) in the spinal cord and are essential for the tonic and reflex control of the cardiovascular system. SPN directly innervate the adrenal medulla and, via postganglionic axons, affect the heart, kidneys, and blood vessels to alter sympathetic outflow and hence blood pressure. Over 80% of bulbospinal, catecholaminergic (C1) neurons contain pituitary adenylate cyclaseactivating polypeptide (PACAP) mRNA. Activation of PACAP receptors with intrathecal infusion of PACAP-38 causes a robust, prolonged elevation in sympathetic tone. Given that a common feature of most forms of hypertension is elevated sympathetic tone, this study aimed to determine in the spontaneously hypertensive rat (SHR) and the Wistar Kyoto rat (normotensive control) 1) the proportion of C1 neurons containing PACAP mRNA and 2) responsiveness to intrathecal PACAP-38. We further investigated whether intrathecal infusion of the PACAP antagonist, PACAP(6 -38), reduces the hypertension in the SHR. The principal findings are that 1) the proportion of PACAP mRNA-containing C1 neurons is not different between normotensive and hypertensive rats, 2) intrathecal PACAP-38 causes a strain-dependent, sustained sympathoexcitation and tachycardia with variable effects on mean arterial pressure in normotensive and hypertensive rats, and 3) PACAP(6 -38) effectively attenuated the effects of intrathecal PACAP-38, but had no effect alone, on any baseline variables. This finding indicates that PACAP-38 is not tonically released in the spinal cord of rats. A role for PACAP in hypertension in conscious rats remains to be determined. sympathetic activity; spinal cord; pituitary adenylate cyclase-activating polypeptide THE ROSTRAL VENTROLATERAL MEDULLA (RVLM) is crucial for the tonic and reflex control of the cardiovascular system (see Refs. 15 and 43 for reviews). RVLM presympathetic neurons are commonly defined as being inhibited following baroreceptor activation and having a spinal axon (2, 28, 29). Neurochemically, 60 -80% of presympathetic neurons are C1 neurons (29,42,48,49), having all of the enzymes required for adrenaline synthesis. Presympathetic RVLM neurons project monosynaptically to sympathetic preganglionic neurons (SPN) in the intermediolateral (IML) cell column of the spinal cord (34,38). SPN, in turn, regulate the activity of the heart, kidneys, blood vessels, and adrenal chromaffin cells, thereby determining sympathetic outflow and ultimately blood pressure.Pituitary adenylate cyclase-activating polypeptide (PACAP) is an excitatory 38-amino-acid peptide originally identified in ovine hypothalamus (32) that also exists as a...

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Section: Discussionmentioning

confidence: 99%

Intrathecal PACAP-38 causes increases in sympathetic nerve activity and heart rate but not blood pressure in the spontaneously hypertensive rat

Farnham

Inglott

Pilowsky

2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…Type II binding sites, which are abundant in various peripheral organs, including the lung, duodenum, and thymus, possess similar affinity for PACAP and VIP (K d Ϸ 1 nM) Lam et al, 1990). Subtle differences in the ability of PACAP38 and PACAP27 to displace 125 I-PACAP27 from its recognition sites in the CNS suggest that the C-terminal extremity of PACAP must contribute to the binding of the peptide to its receptors (Cauvin et al, 1991;Robberecht et al, 1991b). Likewise, type II binding sites have been subdivided into two classes depending on their affinity for secretin (Hubel, 1972) and helodermin : classic VIP binding sites exhibit low affinity for secretin Robberecht et al, 1982Robberecht et al, , 1988, whereas helodermin-preferring binding sites possess higher affinity for helodermin than for VIP or PACAP and no affinity for secretin (Robberecht et al, 1984(Robberecht et al, , 1988Gourlet et al, 1991a;Shima et al, 1996;Solano et al, 1996;Laburthe and Couvineau, 2002;Laburthe et al, 2007).…”

Section: A Pharmacological Characterization Of Pituitary Adenylate Cmentioning

confidence: 99%

“…8) (Cauvin et al, 1991;Masuo et al, 1991;Suda et al, 1991;Masuo et al, 1992;Hou et al, 1994;Zawilska et al, 2003;Jolivel et al, 2009). Significant densities of type I binding sites are also present in the cerebellum (Basille et al, 1993 and pons (Cauvin et al, 1991; ͔VIP (1-7)/GHRH (8-27) VPAC2-R Ro 25-1392 (Xia et al, 1997) Antagonists PAC1-R des(24-42)Maxadilan (M65) (Moro et al, 1999) PACAP(6-38) Weak VPAC2-R agonist (Robberecht et al, 1992b) Hydrazides No information regarding VPAC1/VPAC2-R (Beebe et al, 2008) ͓Sar…”

Section: E Distribution Of Pituitary Adenylate Cyclaseactivating Polmentioning

confidence: 99%

“…͔VIP(6-23) Weak affinity for VPAC2-R (Tams et al, 2000) PG 97-269 Weak affinity for VPAC2-R (Gourlet et al, 1997a;Dickson et al, 2006b) VPAC2-R PG 99-465 VPAC1-R agonist (Moreno et al, 2000) PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE Ogawa et al, 1985;Staun-Olsen et al, 1985;Martin et al, 1987;Cauvin et al, 1991;Suda et al, 1991;Vertongen et al, 1997b;Joo et Dentate gyrus ϩϩϩ -/ϩϩϩ Besson et al, 1984;De Souza et al, 1985;Besson et al, 1986;Martin et al, 1987;Masuo et al, 1991;Vertongen et al, 1997b Masuo et al, 1992). In the rat CNS, type II binding sites are mainly located in the olfactory bulb, the cerebral cortex, the dentate gyrus, the pineal gland, and the thalamus (Table 5) (Besson et al, 1984(Besson et al, , 1986Martin et al, 1987;Vertongen et al, 1998).…”

Section: E Distribution Of Pituitary Adenylate Cyclaseactivating Polmentioning

confidence: 99%

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Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

et al. 2009

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“…PAC 1 , or PACAPselective receptors, bind both active forms of PACAP, PACAP-27 and PACAP-38, with equally high affinities but bind VIP with much lower affinity (26), whereas nonselective VPAC (VPAC 1 and VPAC 2 ) receptors recognize PACAP-27, PACAP-38, and VIP with similar high affinities (27)(28)(29)(30)(31)(32)(33). At least seven isoforms of the PAC 1 receptor exist due to alternative splicing of the mRNA, whereas no splice variants of VPAC 1 or VPAC 2 are presently known to exist.…”

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confidence: 99%

VPAC Receptor Modulation of Neuroexcitability in Intracardiac Neurons

DeHaven

Cuevas

2004

Journal of Biological Chemistry

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Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) have been found within mammalian intracardiac ganglia, but the cellular effects of these neuropeptides remain poorly understood. Fluorometric calcium imaging and whole cell patch clamp recordings were used to examine the effects of PACAP and VIP on [ Pituitary adenylate cyclase-activating polypeptide (PACAP) 1 and vasoactive intestinal polypeptide (VIP) are pleiotropic neuropeptides that belong to the glucagon/secretin/growth hormone-releasing factor family of peptides (1-4). These neuropeptides have pronounced effects on the central nervous system as well as on neurons and effector targets of the autonomic nervous system. For example, in the central nervous system, PACAP is involved in hippocampal synaptic plasticity and associative learning in mice (5), whereas VIP has been shown to regulate intrathalamic rhythm activity and may modulate information transfer through the thalamocortical circuit (6). In the peripheral nervous system, PACAP and VIP appear to play a major role in autonomic regulation of the cardiovascular system. VIP has been shown to cause positive chronotropic and inotropic effects (7-9). In contrast, PACAP has been shown to cause a transient increase in sinus rate and atrial contractility that is followed by negative chronotropic and inotropic responses in isolated canine atria (10). Also, both PACAP and VIP are potent dilators of coronary arteries (11,12). Whereas these neuropeptides can directly influence cardiac tissues, the effects of PACAP and VIP on the heart are in part due to neuroregulatory effects on parasympathetic intracardiac ganglia (9,10,13,14).Mammalian intracardiac ganglia play a major role in neuronal control of the heart and are believed to be capable of independently monitoring and influencing cardiac function. A variety of neurotransmitters and neuromodulators, including PACAP and VIP, appear to be involved in the relaying of information within intracardiac ganglia and onto effector targets such as cardiac valves, coronary arteries, and cardiomyocytes. PACAP and VIP have been detected by immunocytochemistry in nerve fibers in the heart, coronary vasculature, and cardiac parasympathetic ganglia (15)(16)(17)(18)(19)(20). Although extrinsic fibers may be one source of these neuropeptides in the heart (21), PACAP and VIP are also found in cell bodies and nerve fibers of intrinsic cardiac neurons (15)(16)(17)(18)(19)(20). Despite the fact that data clearly demonstrate that these endogenous neuropeptides are potent regulators of the cardiovascular system, the cellular mechanisms mediating their effects remain poorly understood. There are also conflicting reports in the literature concerning the mechanisms by which PACAP and VIP regulate the function of intrinsic cardiac neurons. For example, it has been suggested that PACAP and VIP modulate neurotransmission

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Properties and distribution of receptors for pituitary adenylate cyclase activating peptide (PACAP) in rat brain and spinal cord

Cited by 91 publications

References 19 publications

Intrathecal PACAP-38 causes increases in sympathetic nerve activity and heart rate but not blood pressure in the spontaneously hypertensive rat

Intrathecal PACAP-38 causes increases in sympathetic nerve activity and heart rate but not blood pressure in the spontaneously hypertensive rat

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

VPAC Receptor Modulation of Neuroexcitability in Intracardiac Neurons

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