α-Adrenoceptor agonists and the Ca2+-dependence of smooth muscle contraction: evidence for subtypes of receptors or for agonist-dependent differences in the agonist-receptor interaction?

Abstract

1. The effects of varying [Ca2+]o on the contraction of smooth muscle by different α-adrenoceptor agonists were examined on rat isolated anococcygeus muscle. Agonists were tested in the presence of various [Ca2+]o or ‘Ca2+-re-addition curves’ were constructed. In some experiments the [Ca2+]free was buffered with EGTA and nitrilotriacetic acid. The components of the response which were revealed were further analysed by using drugs which modify Ca2+ mobilization. 2. Three separate elements in the contractile response were identified: (i) an initial transient contraction, due to intracellular Ca2+ release could be isolated with [Ca2+]o between 1 nmol/l and 3 μmol/l (this could be obtained only with noradrenaline, phenylephrine and amidephrine); (ii) a nifedipine-sensitive response requiring [Ca2+]o of 3 μmol/l or more; (iii) a nifedipine-resistant response requiring [Ca2+]o of 100 μmol/l or more. Presumably (ii) and (iii) involve the entry of Ca2+o: they could be obtained with all agonists tested, including these above, methoxamine, indanidine and xylazine. 3. The results are discussed in relation to the possibility of distinct types of response and their relationship to subgroups of receptors or agonists. It is concluded that there is a continuous spectrum of activity across the agonist range and that this is likely to correlate with ‘efficacy’ at a single α1 receptor type.