Effect of calcium antagonists on the response to noradrenaline in the whole and bisected rat vas deferens.
1. The present study was carried out to look at the effect of different calcium antagonists on the response to noradrenaline in the whole and bisected rat vas deferens considering that the response consisted of three components (I) the phasic response (II) the tonic response and (III) the spikes (rhythmic contractions). 2. Nifedipine (3 x 10(-9)-1 x 10(-7) M) inhibited all the components at the same concentration range, verapamil (1 x 10(-7)-1 x 10(-5) M) inhibited the phasic and tonic response but not the rhythmic activity. This latter component, at a certain concentration range and especially in the prostatic portion was markedly potentiated. Diltiazem and flunarizine lay in an intermediate position. 3. Papaverine, a Ca2+ antagonist that acts mainly intracellularly, inhibited preferentially the tonic component; ryanodine was practically inactive. 4. Cromakalim inhibited only partially the phasic and tonic components but totally inhibited the rhythmic contractions. 5. These results can be explained by postulating two types of calcium channels opened by alpha-adrenoceptor stimulation. The first one is verapamil- and nifedipine-sensitive and allows the entry of Ca2+ directly available for the contraction and responsible for the phasic and partially responsible for the tonic component. The second channel is merely nifedipine-sensitive and allows the entry of Ca2+ trigger which can release Ca2+ from intracellular sites: the mobilized Ca2+ is able to sustain the tonic component and is the main one responsible for the rhythmic activity. There is the possibility that this second channel is associated with ATP-sensitive K+ channels.
Boselli
C
C
Istituto di Farmacologia, Facoltà di Farmacia, Università di Pavia, Italy.
Bianchi
L
L
Barbieri
A
A
Grana
E
E
D000818:Animals; D002121:Calcium Channel Blockers / Q000145:classification / Q000494:pharmacology; D019806:Cromakalim / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D005444:Flunarizine / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D009924:Organ Culture Techniques; D010208:Papaverine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014649:Vas Deferens / Q000187:drug effects*
D002121:Calcium Channel Blockers; D019806:Cromakalim; D010208:Papaverine; D004110:Diltiazem; D009543:Nifedipine; D005444:Flunarizine; D009638:Norepinephrine