Effects of Ryanodine and Nifedipine on Contractions Induced by Norepinephrine, Acetylcholine, and Potassium in the Isolated Vas Deferens of the Guinea Pig

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In the present study we tried to determine the relative contributions of sarcoplasmic reticulum (SR) calcium release and gated calcium entry through voltage-dependent calcium-channels (VDC) to the contractions induced by norepinephrine (NE, 10 μM) and acetylcholine (ACh, 10 μM) in the vas deferens of the guinea pig. NE and ACh at 10μM caused contractions composed of three phases : a prephasic, a phasic and a tonic component. Nifedipine strongly inhibited the contractions induced by potassium (K, 100mM) and abolished phasic components of the contractions induced by NE or ACh. However, the tonic components of NE- or ACh-induced contractions were slightly attenuated by nifedipine. Pretreatment with ryanodine in combination with caffeine attenuated prephasic and tonic components of the contractions induced by NE and ACh in a dose-dependent manner. The inhibitory effects of ryanodine and caffeine on the phasic component of NE-induced contractions were divided into two types : 1) abolishment of the phasic contractions and 2) a delayed appearance of the phasic contractions without attenuation of magnitude. However, ryanodine with caffeine minimally affected phasic component by ACh-and K-induced contractions. Ryanodine pretreatment in combination with NE, ACh or K had no effect on the contractions induced by each agonist. These results suggest that 1) SR Ca release is essential for the initiation and/or the maintenance of the tonic components of NE- or ACh-induced contractions as well as for the initiation of the prephasic components, 2) the phasic components by NE depend on both the SR Ca release and gated Ca entry but those induced by ACh depend only on gated Ca entry, 3) the Ca-induced Ca-release mechanism may be scarcely involved in SR Ca release induced by NE and ACh.