Responses Of Rat Vas Deferens Research Articles

Feedback inhibition of responses of rat vas deferens to twin pulse stimulation

Application of a pair of identical pulses of field stimulation to the rat isolated vas deferens results in two responses, the second of which is always smaller than the first, the reduction being inversely related to the internal between the pulses. This effect is due, in part, to the negative feedback inhibition of noradrenaline release, an event which has been demonstrated in a variety of noradrenergically innervated tissues. The ratio of the second response to the first response (the B/A ratio), is increased by substances with antagonistic activity at prejunctional α 2-receptors, and decreased by inhibitors of the neuronal uptake process. The procedure allows an estimate of the relative activity of antagonists at prejunctional α-receptors.

Effect of islet-activating protein (IAP) on α-adreno-ceptors-mediated contractile responses of rat vas deferens

The influence of IAP on the contractile responses of vas deferens to exogenous norepinephrine (NE) and electric stimulation (ES) and the inhibitory effect of Clonidine on the ES-induced contractile responses were investigated to explore the role of Ni in the presynaptically located α2-receptor regulating the release of NE and the postsynaptically located ctl-receptor on the contractile response to NE.

Photoaffinity labeling of opioid receptor with morphine-7,8-oxide (Morphine epoxide)

The opioid receptor mediating inhibitory action of morphine in the electrically stimulated guinea pig ileum was irreversibly photoinactivated by morphine epoxide (3 × 10 −6). Morphine epoxide (up to 3 × 10 −5 M) did not influence the responses of rat vas deferens (ϵ-receptor) or rabbit vas deferens (κ-receptor) to electrical stimulation. Effective concentrations of morphine epoxide were much lower in the guinea pig ileum (μ-receptor) than in the mouse vas deference (δ-receptor). The inhibitory action of [Met]-enkephalin on the twitch responses of the rat vas deferens and mouse vas deferens to electrical stimulation were not influenced after irradiation in the presence of morphine epoxide (3 × 10 −6 M). Therefore, morphine epoxide is probably a useful probe for photoaffinity labeling of the μ-receptor in vitro.

ROLE OF α-ADRENERGIC RECEPTORS IN DENERVATION SUPERSENSITIVITY OF RAT VAS DEFERENS

AbstractContractile responses of rat vas deferens were studied with particular attention directed to the role of receptors and neuronal control. Marked contraction of the vas deferens was observed with α-adrenergic agonists, depending on their concentrations. This tissue had a low sensitivity to ACh. Four days after denervation, this tissue showed a supersensitivity to α-adrenergic agonists and a high K+ concentration, but not to ACh. The increase in sensitivity to α-agonists resulted in an enhancement of the maximal response and a shift of the concentration response curve to lower concentrations of these reagents. Alterations were seen in the α-adrenergic receptors in the rat vas deferens, assayed by measuring the binding of [3H]WB4101. The maximal binding sites decreased significantly to 86 from 142 fmoles per mg protein. The affinity of the receptors for α-agonist, determined by measuring the ability of agonists to displace bound [3H] WB4101, increased significantly, while the affinity to α-antagonists remained unchanged. Studies on [3H]QNB binding indicated no significant change in muscarinic ACh receptors after denervation. Thus, supersensitivity of the α-adrenergic mechanism mediated by a specific change in affinity of α-receptors occurs after denervation of rat vas deferens. These changes in sensitivity and in receptors are discussed in relation to the characteristics and roles of α-receptors in the rat vas deferens.

Role of .ALPHA.-adrenergic receptors in denervation supersensitivity of rat vas deferens.

Contractile responses of rat vas deferens were studied with particular attention directed to the role of receptors and neuronal control. Marked contraction of the vas deferens was observed with alpha-adrenergic agonists, depending on their concentrations. This tissue had a low sensitivity to ACh. Four days after denervation, this tissue showed a supersensitivity to alpha-adrenergic agonists and a high K+ concentration, but not to ACh. The increase in sensitivity to alpha-agonists resulted in an enhancement of the maximal response and a shift of the concentration response curve to lower concentrations of these reagents. Alterations were seen in the alpha-adrenergic receptors in the rat vas deferens, assayed by measuring the binding of [3H]WB4101. The maximal binding sites decreased significantly to 86 from 142 fmoles per mg protein. The affinity of the receptors for alpha-agonist, determined by measuring the ability of agonists to displace bound [3H] WB4101, increased significantly, while the affinity to alpha-antagonists remained unchanged. Studies on [3H]QNB binding indicated no significant change in muscarinic ACh receptors after denervation. Thus, supersensitivity of the alpha-adrenergic mechanism mediated by a specific change in affinity of alpha-receptors occurs after denervation of rat vas deferens. These changes in sensitivity and in receptors are discussed in relation to the characteristics and roles of alpha-receptors in the rat vas deferens.

Increase in response and number of α-adrenoceptors of rat vas deferens on brief pretreatment with an α-agonist

The contractile response of rat vas deferens to epinephrine (E) was enhanced by preincubation with E. After pretreatment with E, there was no significant change in the ED 50 of E but there was a significant increase in the maximum response (39%). There was no change in the cholinergic response after the pretreatment. α-Adrenoceptors in control and E-treated tissues were assessed by measuring [ 3H]WB-4101 binding. Treatment with E resulted in a 27% increase in the number of α-adrenoceptors, but no change in muscarinic acetylcholine receptors measured with [ 3H] quinuclidinyl benzilate. These results are discussed in relation to the response of α-adrenoceptors to the agonist.

Calcium antagonists and contractile responses in rat vas deferens and guinea pig ileal smooth muscle.

The effect of depletion of extracellular Ca2+ (Ca2+ext) on the loss of responsiveness of the guinea pig ileal longitudinal muscle (g.p.i.l.m.) and the rat vas deferens (r.v.d.) to K+ and cis-2-methyl-4-dimethylaminomethyl-1,3-dioxolane methiodide (CD), and K+ and noradrenaline (NA), has been examined and compared with the effects of a variety of local anesthetics and calcium antagonists. The results indicate that qualitative similarities are apparent with respect to the dependence of agonist-induced activity on Ca2+ext in both the g.p.i.l.m. and r.v.d. Distinct differences, however, in the Ca2+ translocation processes in these two tissues, in response to the different agonists, can be shown by the use of a variety of 'calcium antagonists' thus indicating that such translocation processes are both tissue and agonist selective. It is thus noted that, contrary to the Ca2+ depletion studies, D 600 and the usually more potent BAY-1040 showed no discrimination of action or potency in their ability to inhibit components of the NA response in the r.v.d. In contrast, D 600 and the more potent BAY-1040 selectively inhibited the tonic component of the K+ response. Treatment with SKF 525A and parethoxycaine (PC) in the g.p.i.l.m. and SKF 525A in the r.v.d. resulted in a nonselective inhibition of responses of the tissues to all stimulants. However, in the r.v.d. PC potentiated NA action, and its methobromide (MeBr) derivative potentiated both NA and K+ action and also, like PC, partially shifted to the left the dose-response curve to Ca2+ in NA-depolarizing Ca-free Tyrode's. The quaternary MeBr and the tertiary 2-chloroethyl (2Cl) derivatives of SKF 525A and PC were selectively more effective against CD- than K+ supported contractile activity in the g.p.i.l.m. and the 2Cl derivatives were more effective against NA than K+ responses in the r.v.d. The 2Cl derivative of PC also was more effective in antagonizing the Ca2+ dose-response curve in high-CD or high-NA than in high-K+ Ca2+-free Tyrode's.

The effects of lanthanum and thulium on the mechanical responses of rat vas deferens.

1. The contractile responses of rat vas deferens to noradrenaline and K+ are composed of phasic and tonic components both of which are dependent upon the concentration of extracellular Ca2+. 2. Lanthanum, La3+, and thulium ions, Tm3+, inhibited the noradrenaline and K+ induced responses, complete inhibition being obtained at approximately 10(-3) M-Ln3+. 3. La3+ and Tm3+ were equally effective in inhibiting noradrenaline and K+ responses. The phasic and tonic components of the noradrenaline response were equally sensitive to lanthanide cations, Ln3+, but the phasic component of the K+ response was more sensitive than the tonic component. 4. 170Tm binding did not show any saturable component over the concentration range in which inhibition of the pharmacological response was obtained. 5. It is suggested that the actions of Ln3+ in the rat vas deferens are mediated through some kind of membrane stabilization rather than via a specific Ca2+ binding site concerned with excitation-contraction coupling, the mechanism previously postulated for the Ln3+ action in guinea-pig ileal longitudinal muscle.

A comparison of the indirect sympathomimetic actions of tyramine and acetaldehyde in isolated smooth muscle preparations

Rat vas deferens and rabbit aortic strips were used in the present study to compare and contrast the mechanism by which tyramine and acetaldehyde produce contration in smooth muscle. Tetrodotoxin abolished contractile responses in rat vas deferens induced by transmural stimulation, but not by addition of tyramine or acetaldehyde. This indicated that the ability of tyramine and acetaldehyde to produce contraction does not depend upon propagation of the nerve impulse. The ability of acetaldehyde to release transmitter from the tissue was also studied and compared to tyramine in isolated rabbit aortae previously exposed to [ 14C]norepinephrine. Omitting calcium from the bathing solution did not alter the ability of either agent to release radioactivity from aortae. Similar amounts of [ 14C]norepinephrine and 14C-deaminated metabolites were recovered from the efflux media during exposure to acetaldehyde and tyramine. This finding suggests that these agents utilize the same pool of endogenous transmitter to produce their sympathomimetic effects. On the other hand, differences were found in the manner in which tyramine and acetaldehyde gain access to transmitter stores. The ability of tyramine to increase loss of radioactivity from aortae was antagonized by exposure of tissues to cocaine, ouabain, and cold (4°C). Acetaldehyde-evoked loss of radioactivity was not altered by these procedures. Whereas it is clear that tyramine utilizes the neuronal uptake mechanism, acetaldehyde appears to diffuse across the membrane by virtue of its lipid solubility in order to gain access to the same tissue transmitter storage sites.

The mechanism of supersensitivity to norepinephrine induced by cocaine in rat isolated vas deferens

The influence of cocaine on the response of rat vas deferens to norepinephrine, angiotensin, acetylcholine, K + and Ba ++ was examined. Cocaine produced a significant elevation of maximum response to norepinephrine as well as left-ward shift of the dose-response curve. The effect of cocaine on the dose-response curves for angiotensin, acetylcholine and K + was mainly reflected in the enhancement of maximum responses. The contractility of rat vas deferens was extremely dependent upon calcium concentration in the medium, and cocaine lowered the threshold concentration of calcium required for contraction. The findings lead to the conclusion that cocaine potentiates the effect of norepinephrine in at least two different ways: (1) a presynaptic inhibition of norepinephrine uptake, and (2) a postsynaptic direct action which is nonspecific.