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Developmental changes in β‐adrenoceptors, muscarinic cholinoceptors and Ca 2+ channels in rat ventricular muscles
Author(s) -
Kojima Michio,
Ishima Tsuyoshi,
Taniguchi Norihisa,
Kimura Kiyoshi,
Sada Hideaki,
Sperelakis Nicholas
Publication year - 1990
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.1476-5381.1990.tb14704.x
Subject(s) - muscarinic acetylcholine receptor , endocrinology , medicine , acetylcholine , muscle contraction , neuroscience , chemistry , biology , receptor
1 In an attempt to explain the previous electrophysiological data on the ontogeny of β‐adrenergic and muscarinic cholinergic interactions on cardiac Ca 2+ current, biochemical studies were performed on the ontogeny of β‐adrenoceptors, muscarinic cholinoceptors and Ca 2+ channels in cardiac muscle of developing rats: 16–20 days old foetuses, 0–20 days old neonates, and 2–3 months old adults. 2 Developmental changes in cardiac β‐adrenoceptors, muscarinic cholinoceptors, and Ca 2+ channels were determined with the use of specific radioligands, [ 3 H]‐dihydroalprenolol (DHA), [ 3 H]‐quinuclidinyl benzilate (QNB), and [ 3 H]‐nitrendipine (NTD), respectively. 3 The B max value (fmol mg −1 tissue) for [ 3 H]‐DHA binding started to increase on post‐gestation day 20, reached almost its maximum level on neonatal day 6, kept almost the same level until neonatal day 20, and then decreased slightly to its adult level. 4 The B max value (fmol mg −1 tissue) for [ 3 H]‐QNB binding started to increase on post‐gestation day 16, reached almost its maximum level on neonatal day 0, remained almost constant until neonatal day 15, and then decreased to its adult level. 5 The B max value (fmol mg −1 tissue) for [ 3 H]‐NTD binding increased with age between post‐gestation day 18 and neonatal day 15, stayed almost constant until neonatal day 20, and then decreased to its adult level. 6 The K d values for [ 3 H]‐DHA, [ 3 H]‐QNB, and [ 3 H]‐NTD bindings remained almost constant during the developmental period examined. 7 Isoprenaline (Iso) increased the of slow action potentials (APs) from post‐gestation day 18, and the adult level was reached at about 2 weeks after birth; this developmental time course is similar to that of Ca 2+ channels. The number of β‐adrenoceptors also started to increase a few days before birth, but attained its peak about one week earlier than did the of slow APs or the number of Ca 2+ channels. 8 Acetylcholine (ACh) almost completely abolished the Iso‐induced increase in observed from post‐gestation day 18 to neonatal day 20; this developmental time course for the ACh effect is consistent with the finding that the number of muscarinic cholinoceptors started to increase on post‐gestation day 16 and reached a peak on the day of birth. 9 Previous electrophysiological and the present biochemical findings strongly suggest that the functional coupling between muscarinic cholinoceptors and Ca 2+ current is already established when the coupling between β‐adrenoceptors and Ca 2+ current starts to operate in developing rat hearts.