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Surgical Sympathetic Denervation Increases α 1 Adrenoceptor‐Mediated Accumulation of myo‐Inositol Trisphosphate and Muscle Contraction in Rabbit Iris Dilator Smooth Muscle
Author(s) -
Akhtar Rashid A.,
AbdelLatif Ata A.
Publication year - 1986
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1986.tb12930.x
Subject(s) - medicine , denervation , contraction (grammar) , endocrinology , inositol trisphosphate , inositol , muscle contraction , prazosin , chemistry , dilator , skeletal muscle , biology , receptor , antagonist
Sympathetic denervation of the iris muscle produces increases in both the breakdown of phosphati‐dylinositol 4,5‐bisphosphate (PIP 2 ) 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 (IP 3 ) 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 EC 50 values (μ M ) for NE‐induced IP 3 accumulation in normal and denervated dilators were 14 and 3, respectively. This accumulation of IP 3 was blocked by prazosin (1μ M ). (2) The EC 50 values (μ M ) 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 (1μ M ). (3) The t 1/2 values (s) for IP 3 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 ‐[ 3 H]inositol, but not from 32 P or [ 14 C]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 Ca 2+ ‐ATPase increased in the denervated muscle. It is concluded that sympathetic denervation of the iris dilator renders the coupling between α 1 receptors and PIP 2 breakdown into IP 3 and 1,2‐diacylglycerol (DG) more efficient. The NE‐stimulated hydrolysis of PIP 2 could then bring about Ca 2+ mobilization, necessary for muscle contraction, either directly by causing plasma membrane depolarization or indirectly by IP 3 releasing Ca 2+ from sarcoplasmic reticulum and by DG activating protein kinase C, or both.