SRIF receptor subtype expression and involvement in positive and negative contractile effects of somatostatin-14 (SRIF-14) in ventricular cardiomyocytes.
OBJECTIVE
Somatostatin-14 (SRIF-14), a neuropeptide co-stored with acetylcholine in the cardiac parasympathetic innervation, exerts both positive and negative influences directly on contraction of ventricular cardiomyocytes, indicative of involvement of more than one of five known SRIF (SSTR) receptor subtypes. The aim was to characterize receptor subtype expression in adult rat ventricular cardiomyocytes and to investigate the influence of a series of SRIF (SSTR) subtype-selective agonists on contractile parameters.


METHODS
mRNA and protein expression of each receptor subtype were quantified by RT-PCR and immunoblotting respectively; for contraction studies, cells were stimulated at 0.5 Hz under basal conditions and in the presence of isoprenaline (ISO, 10(-8)M).


RESULTS
all five SRIF (SSTR) receptor subtypes were expressed in cardiomyocytes although SRIF1A (SSTR2) and SRIF2A (SSTR1) were less abundant than the other subtypes. L803087 (10(-8)M), a SRIF2B (SSTR4) agonist, attenuated ISO-stimulated peak contractile amplitude and prolonged relaxation time (T(50)). L796778 (10(-7)M), a SRIF1C (SSTR3) agonist, augmented basal and ISO-stimulated peak contractile amplitude; L779976 (10(-8)M) and L817818 (10(-9)M), agonists at SRIF1A (SSTR2) and SRIF1B (SSTR5) receptors, respectively, also augmented ISO-stimulated peak amplitude.


CONCLUSIONS
These data support involvement of SRIF2B (SSTR4) receptors in the negative contractile effects of SRIF-14, while one or more of the three SRIF1 receptor subtypes (SSTR2, 3 or 5) may contribute to the positive contractile effects of SRIF-14.
Bell
David
D
Division of Medicine and Therapeutics, School of Medicine, Dentistry and Biomedical Sciences, The Queen's University of Belfast. d.bell@qub.ac.uk
Zhao
Youyou
Y
McMaster
Brian
B
McHenry
Eugene M
EM
Wang
Xuanhui
X
Kelso
Elizabeth J
EJ
McDermott
Barbara J
BJ
D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D006352:Heart Ventricles / Q000166:cytology*; D006984:Hypertrophy; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism*; D013997:Time Factors
D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D013004:Somatostatin; D007545:Isoproterenol