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PACAP and VIP have prominent effects on cardiac function in several species, but little is known about their influence on the murine heart. Accordingly, we evaluated the expression of PACAP/VIP receptors in mouse heart and the response of isolated atria to peptide agonists. Quantitative PCR demonstrated that PAC₁, VPAC₁, and VPAC₂ receptor mRNAs are present throughout the mouse heart. Expression of all three receptor transcripts was low, PAC₁ being the lowest. No regional differences in expression were detected for individual receptor mRNAs after normalization to L32. Pharmacological effects of PACAP-27, VIP, and the selective PAC₁ agonist maxadilan were evaluated in isolated, spontaneously beating atria from C57BL/6 mice of either sex. Incremental additions of PACAP-27 at 1 min intervals caused a concentration-dependent tachycardia with a logEC₅₀=-9.08 ± 0.15 M (n=7) and a maximum of 96.3 ± 5.9% above baseline heart rate. VIP and maxadilan also caused tachycardia but their potencies were about two orders of magnitude less. Increasing the dosing interval to 5 min caused a leftward shift of the concentration-response curve to maxadilan but no changes in the curves for PACAP-27 or VIP. Under this condition, neither the potency nor the efficacy of maxadilan differed from those of PACAP-27. Neither PACAP-27 nor maxadilan caused tachyphylaxis, and maximal responses to maxadilan were maintained for at least 2 h. We conclude that all three VIP/PACAP family receptors are expressed by mouse cardiac tissue, but only PAC₁ receptors mediate positive chronotropic responses to PACAP-27 and VIP.

Titel:	PAC₁ receptors mediate positive chronotropic responses to PACAP-27 and VIP in isolated mouse atria.
Autor/in / Beteiligte Person:	Hoover, DB ; Girard, BM ; Hoover, JL ; Parsons, RL
Link:	Zum Volltext
Zeitschrift:	European journal of pharmacology, Jg. 713 (2013-08-05), Heft 1-3, S. 25
Veröffentlichung:	2005- : Amsterdam : Elsevier Science ; <i>Original Publication</i>: Amsterdam, North Holland Pub. Co., 2013
Medientyp:	academicJournal
ISSN:	1879-0712 (electronic)
DOI:	10.1016/j.ejphar.2013.04.037
Schlagwort:	Animals Dose-Response Relationship, Drug Female Gene Expression drug effects Heart Atria metabolism In Vitro Techniques Male Mice Mice, Inbred C57BL RNA, Messenger genetics RNA, Messenger metabolism Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I agonists Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I genetics Receptors, Vasoactive Intestinal Peptide, Type II agonists Receptors, Vasoactive Intestinal Peptide, Type II genetics Receptors, Vasoactive Intestinal Polypeptide, Type I agonists Receptors, Vasoactive Intestinal Polypeptide, Type I genetics Species Specificity Heart Atria drug effects Pituitary Adenylate Cyclase-Activating Polypeptide pharmacology Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I metabolism Receptors, Vasoactive Intestinal Peptide, Type II metabolism Receptors, Vasoactive Intestinal Polypeptide, Type I metabolism Vasoactive Intestinal Peptide pharmacology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Language: English [Eur J Pharmacol] 2013 Aug 05; Vol. 713 (1-3), pp. 25-30. <i>Date of Electronic Publication: </i>2013 May 09. MeSH Terms: Heart Atria / drug effects ; Pituitary Adenylate Cyclase-Activating Polypeptide / pharmacology ; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / metabolism ; Receptors, Vasoactive Intestinal Peptide, Type II / metabolism ; Receptors, Vasoactive Intestinal Polypeptide, Type I / metabolism ; Vasoactive Intestinal Peptide / pharmacology ; Animals ; Dose-Response Relationship, Drug ; Female ; Gene Expression / drug effects ; Heart Atria / metabolism ; In Vitro Techniques ; Male ; Mice ; Mice, Inbred C57BL ; RNA, Messenger / genetics ; RNA, Messenger / metabolism ; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / agonists ; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / genetics ; Receptors, Vasoactive Intestinal Peptide, Type II / agonists ; Receptors, Vasoactive Intestinal Peptide, Type II / genetics ; Receptors, Vasoactive Intestinal Polypeptide, Type I / agonists ; Receptors, Vasoactive Intestinal Polypeptide, Type I / genetics ; Species Specificity References: Br J Pharmacol. 2012 May;166(1):4-17. (PMID: 22289055) ; Naunyn Schmiedebergs Arch Pharmacol. 1996 Oct;354(4):424-30. (PMID: 8897444) ; Clin Sci (Lond). 2001 Dec;101(6):637-43. (PMID: 11724651) ; Am J Physiol Heart Circ Physiol. 2001 Mar;280(3):H1058-65. (PMID: 11179047) ; J Cardiovasc Pharmacol. 1997 Feb;29(2):216-21. (PMID: 9057071) ; Peptides. 1989 Mar-Apr;10(2):343-7. (PMID: 2755874) ; Neurosci Lett. 2002 Aug 2;328(1):45-9. (PMID: 12123856) ; J Comp Neurol. 2000 Jul 17;423(1):26-39. (PMID: 10861534) ; Cell Tissue Res. 2003 Dec;314(3):337-50. (PMID: 14523644) ; Am J Physiol Regul Integr Comp Physiol. 2003 Feb;284(2):R588-97. (PMID: 12414436) ; J Physiol. 2007 Jul 1;582(Pt 1):87-93. (PMID: 17495034) ; J Biol Chem. 1997 Jan 10;272(2):966-70. (PMID: 8995389) ; Neuropeptides. 2011 Feb;45(1):33-42. (PMID: 21035185) ; J Pharmacol Exp Ther. 2009 Oct;331(1):197-203. (PMID: 19602551) ; J Pharmacol Exp Ther. 1997 Nov;283(2):478-87. (PMID: 9353360) ; Regul Pept. 2005 Jul 15;129(1-3):139-46. (PMID: 15927709) ; J Neurosci. 1998 Dec 1;18(23):9766-79. (PMID: 9822736) ; Pharmacol Rev. 2009 Sep;61(3):283-357. (PMID: 19805477) ; J Mol Neurosci. 2012 Nov;48(3):667-73. (PMID: 22648511) ; Auton Neurosci. 2011 Jul 5;162(1-2):24-31. (PMID: 21334985) ; J Biol Chem. 1992 Jan 15;267(2):1062-6. (PMID: 1730635) ; Am J Physiol Heart Circ Physiol. 2001 Oct;281(4):H1667-74. (PMID: 11557557) ; Cardiovasc Res. 2001 Jan;49(1):27-37. (PMID: 11121793) ; Eur J Endocrinol. 2009 Apr;160(4):561-5. (PMID: 19174531) ; J Mol Neurosci. 2010 Nov;42(3):390-6. (PMID: 20428965) ; Eur J Pharmacol. 1996 Nov 21;315(3):289-96. (PMID: 8982667) Grant Information: P20 RR016435 United States RR NCRR NIH HHS; P30 GM103498 United States GM NIGMS NIH HHS; P30 RR032135 United States RR NCRR NIH HHS; P30GM103498 United States GM NIGMS NIH HHS Substance Nomenclature: 0 (Pituitary Adenylate Cyclase-Activating Polypeptide) ; 0 (RNA, Messenger) ; 0 (Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I) ; 0 (Receptors, Vasoactive Intestinal Peptide, Type II) ; 0 (Receptors, Vasoactive Intestinal Polypeptide, Type I) ; 37221-79-7 (Vasoactive Intestinal Peptide) Entry Date(s): Date Created: 20130514 Date Completed: 20140113 Latest Revision: 20211021 Update Code: 20240513 PubMed Central ID: PMC3700323

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PAC₁ receptors mediate positive chronotropic responses to PACAP-27 and VIP in isolated mouse atria.