Effects of Metoclopramide and Isoprenaline in the Rat Vas Deferens; Interactions With Α‐adrenoceptors

Spedding, Michael

doi:10.1111/j.1476-5381.1980.tb10916.x

Cited by 31 publications

(17 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, the hypotensive effect of bromocriptine in the anesthetized dog has been attributed to a peripheral mechanism, 32 which suggests a possible species difference between the SHR and the dog. Since both bromocriptine and metoclopramide are not selective and act on DA and other receptors, 33 -34 further studies are required to prove that the hypotensive effects of bromocriptine are solely the result of action on central DA receptors.…”

Section: Discussionmentioning

confidence: 99%

Selective antagonism of the hypotensive effects of dopamine agonists in spontaneously hypertensive rats.

McCoy¹,

Douglas²,

Goldberg³

1986

Hypertension

View full text Add to dashboard Cite

SUMMARY Agonists of dopamine receptors can lower blood pressure by vasodilation through action on dopamine) receptors, inhibition of sympathetic nerve activity by action on dopamine 2 receptors, or actions in the central nervous system. Fenoldopam, a selective dopamine, agonist, piribedil, a selective dopamine 2 agonist, and dipropyl dopamine, a mixed dopamine, and dopamine 2 agonist, were injected intravenously in pentobarbital-anesthetized, spontaneously hypertensive rats (SHR). The mechanism for the antihypertensive effect was evaluated by administration of the selective dopamine, antagonist SCH 23390 and the selective dopamine 2 antagonist domperidone. While SCH 23390 only antagonized the hypotensive effects of fenoldopam, domperidone abolished the fall in blood pressure produced by dipropyl dopamine and piribedil but not by fenoldopam. Increments in heart rate and plasma norepinephrine levels accompanied the hypotensive effects of fenoldopam. The increase in heart rate was abolished by a dose of SCH 23390 sufficient to completely block the hypotensive effects and was significantly attenuated by the ganglionic blocking agent hexamethonium, which suggests that the increase in heart rate was due to a baroreceptor reflex. Fenoldopam does not cross the blood-brain barrier, which suggests that its hypotensive effect was mediated by peripheral dopamine, receptors. Since domperidone does not cross the blood-brain barrier and significantly antagonized the hypotensive and bradycardic effects of dipropyl dopamine and piribedil, these effects were mediated primarily by peripheral dopamine 2 receptors. These results indicate that SCH 23390 and domperidone are useful agents to identify the receptor subtype mediating the action of dopamine agonists in SHR. (Hypertension 8: 298-302, 1986 lease from sympathetic nerve terminals, leading indirectly to vasodilation and a fall in heart rate (HR). 4 Because of these actions, agonists of both receptor subtypes are receiving increasing attention as potential antihypertensive agents. 5 "" Dopamine and most DA agonists act on both DA receptor subtypes and on other receptors in the central nervous system and periphery. 3 8 9 Therefore, it is important to develop an animal model to separate these diverse mechanisms. Several studies have demonstrated that agonists, which may act on DA, or DA 2 receptors, lower blood pressure (BP) in spontaneously hypertensive rats (SHR). 5 ' 12 " u Until recently, selective antagonists were not available to prove that reduction in BP was due to action on either one or both receptor subtypes. The benzazepine SCH 23390 and the butyrophenone domperidone are extremely selective antagonists of DA, and DA 2 receptors, respectively. 15 -' 6 The present experiments were designed to determine whether these selective antagonists inhibit the hypotensive ef-298

show abstract

Section: Discussionmentioning

confidence: 99%

Selective antagonism of the hypotensive effects of dopamine agonists in spontaneously hypertensive rats.

McCoy¹,

Douglas²,

Goldberg³

1986

Hypertension

View full text Add to dashboard Cite

show abstract

“…However (+)butaclamol was significantly (P < 0.001) less potent as an antagonist of phenylephrine-induced contractions in the rat aorta compared with its potency as an antagonist of clonidine in the guinea-pig ileum, indicating a degree of selectivity for a,-adrenoceptors. The finding that (+)-butaclamol had equivalent potency to yohimbine as a n antagonist of a,-adreno-Gptors constitutes further evidence that some forms of dopamine receptor have structural similarities to a,adrenoceptors (Spedding 1980). In this regard, the in vitro potencies of several antagonists which have been used to define the dopamine vascular receptor are similar to their potencies at a,-adrenoceptors ( Table 1).…”

Section: Stereospecific Blockade Of A2-adrenoceptors By (+)-Butaclamolmentioning

confidence: 74%

“…On this basis, (+)-butaclamol has been recently used to define dopamine receptors in the renal (Schmidt & Imbs 1980) and mesenteric (Br0dde & Gross 1980;Brodde et al 1981a, b) vascular beds. However, many dopamine receptor antagonists are potent a-adrenoceptor antagonists showing a variable degree of selectivity for a ' -or a,adrenoceptors (Spedding 1980;Petersen 1981). We have therefore examined the isomers of butaclamol for a-adrenoceptor antagonist activity using phenylephrine-induced contractions of rat aorta to assess effects on a,-adrenoceptors and clonidine-induced inhibition of the responses to field stimulation of guineapig ileum to assess effects on a,-adrenoceptors.…”

Section: Stereospecific Blockade Of A2-adrenoceptors By (+)-Butaclamolmentioning

confidence: 99%

Stereospecific blockade of α2-adrenoceptors by (+)-butaclamol: implications for the characterization of dopamine receptors

Spedding

Berg

1982

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

“…The additional presence of postjunctional 6 2 , but not /j1, adrenoreceptors in this tissue has also recently been described (Von Euler & Hedqvist, 1975;Jenkins, Marshall & Nasmyth, 1977;Vohra, 1979;Lotti, Chang & Kling, 1980). Isoprenaline has been reported to activate postjunctional p2 and a l or prejunctional a2adrenoreceptors in the field stimulated rat vas deferens (Gangly & Bhattacharya, 1969;Vohra, 1979;Lotti et al, 1980;Spedding, 1980). However, quantitative evaluation of each of these activities of isoprenaline under the same conditions and in the presence and absence of endo-genous catecholamines or specific adrenoreceptor antagonists has not been reported and is the subject of the present investigations.…”

Section: Introductionmentioning

confidence: 76%

CHARACTERIZATION OF THE ADRENORECEPTOR ACTIVITIES OF ISOPRENALINE IN THE FIELD STIMULATED RAT VAS DEFERENS: SELECTIVE SUPERSENSITIVITY TO β₂‐MEDIATED RESPONSES FOLLOWING RESERPINE TREATMENT

Lotti

Cerino

Kling

1982

Journal of Autonomic Pharmacology

View full text Add to dashboard Cite

1 Low concentrations of isoprenaline (EC50 = 45.6 nM) inhibited contractions in the isolated field stimulated rat vas deferens. This inhibitory effect was markedly attenuated by the postjunctional beta 2-adrenoreceptor antagonist timolol, but not affected by the prejunctional alpha 2 or postjunctional alpha 1-adrenoreceptor antagonists rauwolscine and prazosin, respectively. 2 In vas deferens of rats previously treated with reserpine, the postjunctional beta 2-adrenoreceptor-mediated inhibitory response to isoprenaline was markedly potentiated. 3 High concentrations of isoprenaline (EC50 = 1.5 microM) also inhibited contractility in tissues in which postjunctional beta 2-adrenoreceptors were maximally blocked by high concentrations of timolol. This contractile inhibition produced by isoprenaline was abolished by rauwolscine but not significantly altered by prazosin or pretreatment of the rats with reserpine indicating stimulation of prejunctional alpha 2-adrenoreceptors. 4 Rauwolscine pretreatment unmasked an ability of isoprenaline (EC50 = 17.1 microM) to produce enhancement of field stimulation-induced contractions. This response was abolished by prazosin but was unaffected by timolol or reserpinization indicating an action upon postjunctional alpha 1-adrenoreceptors. 5 The data indicate isoprenaline activates adrenoreceptor mechanisms in the field stimulated rat vas deferens by a direct action not dependent upon endogenous catecholamines and with an order of activity of beta 2 much greater than alpha 2 greater than alpha 1. Pretreatment with reserpine produces rapid and selective development of supersensitivity to the postjunctional beta 2-mediated inhibitory response of isoprenaline in this preparation.

show abstract

Effects of Metoclopramide and Isoprenaline in the Rat Vas Deferens; Interactions With Α‐adrenoceptors

Cited by 31 publications

References 34 publications

Selective antagonism of the hypotensive effects of dopamine agonists in spontaneously hypertensive rats.

Selective antagonism of the hypotensive effects of dopamine agonists in spontaneously hypertensive rats.

Stereospecific blockade of α2-adrenoceptors by (+)-butaclamol: implications for the characterization of dopamine receptors

CHARACTERIZATION OF THE ADRENORECEPTOR ACTIVITIES OF ISOPRENALINE IN THE FIELD STIMULATED RAT VAS DEFERENS: SELECTIVE SUPERSENSITIVITY TO β₂‐MEDIATED RESPONSES FOLLOWING RESERPINE TREATMENT

Contact Info

Product

Resources

About

Effects of Metoclopramide and Isoprenaline in the Rat Vas Deferens; Interactions With Α‐adrenoceptors

Cited by 31 publications

References 34 publications

Selective antagonism of the hypotensive effects of dopamine agonists in spontaneously hypertensive rats.

Selective antagonism of the hypotensive effects of dopamine agonists in spontaneously hypertensive rats.

Stereospecific blockade of α2-adrenoceptors by (+)-butaclamol: implications for the characterization of dopamine receptors

CHARACTERIZATION OF THE ADRENORECEPTOR ACTIVITIES OF ISOPRENALINE IN THE FIELD STIMULATED RAT VAS DEFERENS: SELECTIVE SUPERSENSITIVITY TO β2‐MEDIATED RESPONSES FOLLOWING RESERPINE TREATMENT

Contact Info

Product

Resources

About

CHARACTERIZATION OF THE ADRENORECEPTOR ACTIVITIES OF ISOPRENALINE IN THE FIELD STIMULATED RAT VAS DEFERENS: SELECTIVE SUPERSENSITIVITY TO β₂‐MEDIATED RESPONSES FOLLOWING RESERPINE TREATMENT