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Noradrenaline‐stimulated inositol phosphate accumulation in arteries from spontaneously‐hypertensive rats
Author(s) -
Guild S.B.,
Jenkinson S.,
Muir T.C.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14425.x
Subject(s) - medicine , endocrinology , inositol , inositol phosphate , chemistry , catecholamine , inositol trisphosphate , dephosphorylation , receptor , biology , phosphorylation , biochemistry , phosphatase
1 The effects of noradrenaline upon polyphosphoinositide (PPI) breakdown was investigated by measuring the accumulation of inositol phosphates (IPs) in tail arteries from normo‐ (WKY) and spontaneously‐hypertensive (SHR) rats. 2 Noradrenaline (10 −7 −10 −3 m ) evoked a concentration‐dependent increase in total IP accumulation in both WKY and SHR rats but no significant differences between the populations were detected. 3 In contrast, significant differences in the accumulation of the individual IPs, which contributed to the total IP, occurred. A significantly greater noradrenaline‐stimulated accumulation of inositol trisphosphate (IP 3 ) was observed in tissues from SHR compared with those from WKY rats at each effective concentration of noradrenaline. This was paralleled by an equivalent reduction in inositol monophosphate (IP 1 ) accumulation, consistent with the lack of a significant difference in noradrenaline‐stimulated total IP accumulation between the two populations. 4 In time course studies, an enhanced noradrenaline‐induced accumulation of IP 3 , in SHR compared to WKY rats, occurred from the earliest time point studied after the addition of the catecholamine both in the presence and absence of LiCL (10 m m ). In the presence of LiCl (10 m m ) no significant difference in noradrenaline‐evoked total IP accumulation between SHR and WKY rats was observed; in the absence of LiCl noradrenaline‐evoked a greater total IP accumulation in SHR than in WKY rats at all time points investigated. 5 These studies suggest that the main reason for the enhanced noradrenaline‐induced accumulation of IP 3 in arteries from SHR rats is a reduced rate of dephosphorylation of both IP 3 and inositol bisphosphate (IP 2 ) rather than a greater formation of IP 3 from PPIs. 6 This enhanced accumulation of IP 3 may result in an increased calcium mobilisation accounting for the increased contractility to noradrenaline of tail arteries from SHR as compared with those from WKY rats.