ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: Sympathetic denervation of the iris muscle produces increases in both the breakdown of phosphati-dylinositol 4,5-bisphosphate (PIP2) and in muscle contraction in response to norepinephrine (NE). To shed more light on the biochemical basis underlying this supersensitivity we investigated: (1) the effects of NE on PIP, breakdown, measured as myoinositol trisphosphate (IP3) accumulation, and on muscle contraction in normal and denervated rabbit iris dilator; and (2) the effects of denervation on selected biochemical properties of this muscle. The data obtained from these studies can be summarized as follows: (1) The EC50 values (μM) for NE-induced IP3 accumulation in normal and denervated dilators were 14 and 3, respectively. This accumulation of IP3 was blocked by prazosin (1μM). (2) The EC50 values (μM) for NE-induced contraction for the normal and denervated muscles were 10 and 0.6, respectively. The NE-induced muscle contraction was blocked by prazosin (1μM). (3) The t1/2 values (s) for IP3 accumulation in normal and denervated muscles were 31 and 11, respectively, and for contraction the values were 19 and 9, respectively. (4) Denervation increased significantly (15–18%) the basallabelling of phosphoinositides from myo-[3H]inositol, but not from 32P or [14C]arachidonic acid. (5) Denervation had little effect on the activities of the enzymes involved in phosphoinositide metabolism. However, the activities of protein kinase C and Ca2+-ATPase increased in the denervated muscle. It is concluded that sympathetic denervation of the iris dilator renders the coupling between α1 receptors and PIP2 breakdown into IP3 and 1,2-diacylglycerol (DG) more efficient. The NE-stimulated hydrolysis of PIP2 could then bring about Ca2+ mobilization, necessary for muscle contraction, either directly by causing plasma membrane depolarization or indirectly by IP3 releasing Ca2+ from sarcoplasmic reticulum and by DG activating protein kinase C, or both.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1471-4159.1986.tb12930.x
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