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A STUDY OF THE ROLE OF CYCLIC ADENOSINE 3′,5′‐MONOPHOSPHATE IN THE DEPRESSION BY OPIATES AND OPIOID PEPTIDES OF EXCITATORY JUNCTION POTENTIALS IN THE MOUSE VAS DEFERENS
Author(s) -
NORTH R.A.,
VITEK L.V.
Publication year - 1980
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.1476-5381.1980.tb10940.x
Subject(s) - ibmx , chemistry , adenosine , endocrinology , phosphodiesterase inhibitor , phosphodiesterase , medicine , vas deferens , excitatory postsynaptic potential , extracellular , biophysics , forskolin , biochemistry , biology , receptor , enzyme
1 Excitatory junction potentials (e.j.ps) were recorded with intracellular microelectrodes from smooth muscle cells of the mouse isolated vas deferens. The amplitude of the e.j.p. was used as a measure of transmitter release evoked by applying single pulse stimuli to the intramural nerves. 2 Cyclic adenosine 3′,5′‐monophosphate (cyclic AMP) and dibutyryl cyclic AMP (db cyclic AMP, up to 1 m m ) depressed the amplitude of e.j.ps, probably by interacting with extracellular sites on the nerve terminals, similar to those responsive to adenosine. 3 The phosphodiesterase inhibitors, 1‐methyl‐3‐isobutyl xanthine (IBMX) and 1‐ethyl‐4‐hydrazino‐1 H ‐pyrazolo(3,4‐b)pyridine‐5‐carboxylic acid, ethylester, hydrochloride (SQ20,006) increased e.j.p. amplitude; this increase was much greater when the phosphodiesterase inhibitor was applied together with db cyclic AMP. 4 Neither the cyclic nucleotides nor the phosphodiesterase inhibitors altered the resting membrane potential of smooth muscle cells. 5 The amplitude of the e.j.p. was depressed by normorphine, d ‐Ala 2 ‐Met 5 ‐enkephalinamide (DAEA) and d ‐Ala 2 ‐ d ‐Leu 5 ‐enkephalin (DADL) with respective EC 50 s of 560 n m , 49 n m and 510 p m . 6 There was no change in the EC 50 for normorphine in the presence of cyclic AMP (1 m m ) or in the presence of a combination of IBMX (50 μ m ) and db cyclic AMP (500 μ m ). Similarly, the depression of the e.j.p. by DAEA or DADL was not affected by the combination IBMX (500 μ m ) and db cyclic AMP (250 μ m ). 7 These findings provide evidence against the hypothesis that a reduction in cyclic AMP levels in nerve terminals is an essential step in the inhibition by opiates and opioid peptides of transmitter release.