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In vitro denervation of the rat vas deferens through hypothermic storage
Author(s) -
Jurkiewicz N.H.,
Garcia A.G.,
Jurkiewicz A.
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.tb12791.x
Subject(s) - vas deferens , medicine , endocrinology , chemistry , tyramine , denervation , barium chloride , acetylcholine , dopamine , histamine , catecholamine , long term potentiation , agonist , biology , receptor , organic chemistry
1 The rat vas deferens was excised, stored at 4–6°C and tested after 24, 48, 72 or 96 h for its contractile activity and for the presence of innervation. 2 The maximal contractile capacity of the vas, tested through cumulative concentrations of barium chloride (3 × 10 −2 m ) was progressively reduced from about 110 mm to about 63 mm after 72 h, without further decay after 96 h. Spontaneous rhythmic contractions were practically absent. 3 A loss of endogenous pools of catecholamines was indicated by four parameters: (a) a decline of about 80% after 24 h and of more than 95% after 48 h of the contractile effect of the indirect sympathomimetic agonist tyramine; (b) a fall of about 20%, 50% and 85% on the concentration of noradrenaline, respectively after 24, 48 and 72 h; (c) a fall of about 25% and 90% after respectively 24 and 48 h, of the activity of dopamine‐β‐hydroxylase (DBH); (d) a decline of noradrenaline‐induced histofluorescence on cross sections of the vas. 4 A loss of neuronal uptake capacity was indicated by: (a) a progressive variation of the apparent affinity for adrenaline, expressed as pD 2 values, that increased by about 1.5 log units (corresponding to a 30 fold potentiation) after 72 h, and (b) a reduction of the ability of cocaine to potentiate the contractile effects of adrenaline. 5 The pD 2 values for barium chloride, 5‐hydroxytryptamine (5‐HT) and histamine were not significantly changed, while the corresponding value for acetylcholine was slightly but significantly reduced by about 0.8 log units. 6 The maximal heights of concentration‐response curves for noradrenaline, acetylcholine, histamine and 5‐HT were reduced by 42–66% in relation to controls. However, when this reduction was measured in relation to the corresponding barium effect, by means of the relative responsiveness ratio (p), a small though significant increase was observed for noradrenaline, and a fall for the other drugs. 7 It is concluded that: (1) the values for the various biochemical and pharmacological parameters decline at different rates, though revealing altogether that denervation is completed by at least 85% after 72 h of hypothermic storage; (2) two of the results, i.e., the lack of spontaneous rhythmic contractions and the lack of increased contractile effects for acetylcholine, 5‐HT and histamine, indicate that in these conditions the vas is devoid of the so‐called nonspecific signs of denervation.