Influence of cooling on the responsiveness of rat isolated anococcygeus muscle to noradrenaline.
The isolated anococcygeus muscle of the rat was used to study the effect of temperature on noradrenaline-induced contraction. The preparation was suspended in an organ bath containing Krebs bicarbonate solution for isometric tension recording. A decrease of the bath temperature from 37 degrees C to 20 degrees C (cooling) produced an increase in tissue sensitivity to noradrenaline, as reflected in a 5.37-fold leftward shift in the concentration-response curve, and increased the maximum contractile response to this agonist (14.3%). Cooling had no effect on tissue sensitivity to a selective alpha 1-adrenoceptor agonist, methoxamine, but increased (12.4%) the maximum contraction to a similar extent to that to noradrenaline. 6-Hydroxydopamine pretreatment or nortriptyline (1 mumol/l) induced a leftward shift of the noradrenaline concentration-response curve at 37 degrees C, and profoundly inhibited the potentiating effect of cooling on tissue sensitivity to the catecholamine; the effect of cooling on the maximum response was unaffected. The affinity of noradrenaline or methoxamine for alpha 1-adrenoceptors at 37 degrees C, determined from its dissociation constant (KA), was not significantly different from that at 20 degrees C. KA values were determined by use of irreversible antagonism with phenoxybenzamine. On the other hand, diltiazem at concentration of 3 mumol/l, which almost completely abolished the calcium ion-induced contraction of the potassium ion-depolarized muscle, caused only slight inhibition in the concentration-response curve for noradrenaline. The contractile responses to Ca2+ of the K+-depolarized muscle and of the tissue incubated in Ca2+ -free (EGTA 0.1 mmol/l) Krebs solution containing diltiazem and noradrenaline were both depressed by cooling.(ABSTRACT TRUNCATED AT 250 WORDS)
Ishii
T
T
Department of Pharmacology, Dokkyo University School of Medicine, Tochigi, Japan.
Machida
N
N
Shimo
Y
Y
D000316:Adrenergic alpha-Agonists / Q000378:metabolism; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003080:Cold Temperature; D004110:Diltiazem / Q000494:pharmacology; D004347:Drug Interactions; D066298:In Vitro Techniques; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014638:Vanadates / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D014638:Vanadates; D004110:Diltiazem; D008729:Methoxamine; D002118:Calcium; D009638:Norepinephrine; D011224:Prazosin